Physiology
Amphibians have two discrete lipid storage organs: coelomic fat bodies, and inguinal fat bodies. Coelomic fat bodies are present in all modern amphibians [
[1]
], whereas the inguinal fat bodies have only been described in some bufonid anurans [[2]
]. Lipids are also stored in various cutaneous and subcutaneous fat deposits, around the heart, in the liver, and in the tail of some plethodontid salamanders. These lipid storage organs function as caloric (energy) depots, allowing the amphibian to accumulate energy during periods of high food availability, and as fatty acid reservoirs, allowing the amphibian to store lipids that may be needed at other times by different tissues undergoing growth or repair. Amphibians are much more efficient than endotherms at converting ingested energy into body mass. An amphibian typically converts at least 40–80% of absorbed energy into body mass, whereas an endotherm typically converts less than 4% of absorbed energy into body mass [[3]
]. Adult amphibians are obligate carnivores, a trophic niche that lacks adaptability to shift metabolism to take advantage of varying proportions of fat, protein, and carbohydrates in the diet. Amphibians preferentially convert carbohydrates or protein to fat making lipids the main depot of energy in the amphibian. In captivity, this preferential accumulation of fat over protein occurred even in captive European toads (Bufo bufo) maintained on a low-calorie diet [[4]
]. Additionally, at extremely low-caloric rations the relative rate of deposition of fat over protein increases! This metabolic cycle is thought to be an adaptation that shifts energy to fat needed for hibernation or aestivation and subsequent reproduction rather than to increasing muscle mass and overall body size [[1]
]. Theoretically, once an amphibian has reached the minimum adult size for reproduction, there is no improvement in the genetic fitness of a large mature amphibian over a small mature amphibian—the majority of accumulated energy is used to support reproduction. In rare cases where there is an advantage to size, it is typically a sexually dimorphic characteristic where the females attain the larger body size to accommodate more eggs, or, in the case of viviparous amphibians, fewer but more advanced offspring. Within the larger size class of a dimorphic species there is actually little variation in the range of body weight.Amphibian coelomic fat bodies are derived from the germinal epithelium, the same embryologic tissue layer as gives rise to the gonads. This origin is unique to amphibians among vertebrates, and supports monophyly of modern amphibians. The anterior portion of a mesenteric fold gives rise to the coelomic fat bodies while the posterior portion becomes the gonads, but the two organs remain independently vascularized [
[1]
]. The majority of lipids are concentrated in the coelomic fat bodies. These organs are proportionately larger in sexually immature amphibians compared to sexually mature amphibians, but the underlying cause of this difference is undetermined [[1]
]. It is likely that there is a shift in the lipid use patterns between the immature and mature amphibian and a subsequent impact on lipid deposition and size of the coelomic fat bodies.In sexually mature amphibians, coelomic fat bodies largely support gonadal growth and maturation over somatic tissues, a theory supported by the inverse relationship between coelomic fat body size and gonadal size [
[1]
]. Amphibians with gonadal atrophy have large coelomic fat bodies, regardless of whether the gonadal atrophy is due to normal seasonal reproductive cycling or surgical extirpation of the pars distalis [[1]
]. Amphibians develop atrophied or degenerate gonads following surgical removal of the coelomic fat bodies.In a healthy, sexually mature, female amphibian with a normal ovarian cycle, lipids are preferentially allocated to support vitellogenesis over deposition into fat depots or use by other tissues [
[1]
]. As oocytes mature and grow, fat bodies decrease in size. Vitellogenesis depends on nutrient intake in excess of the standard metabolic rate, and thus ovarian growth depends entirely on food availability. If vitellogenesis is entirely supported by food intake and additional energy is still available, the coelomic fat bodies may accumulate additional lipid. If a sexually mature female amphibian does not initiate a normal ovarian cycle, the coelomic fat bodies and other fat depots accumulate the lipids that the ovaries would normally use for vitellogenesis. In the wild, an immature female amphibian may reach the size of sexually mature female too late in the season to be cued into the ovarian cycle, and will thus retain large coelomic fat bodies “out of season.” In most temperate amphibians, the ovarian cycle resumes following hibernation with increasing temperatures and increasing day length photoperiod, although a few species initiate vitellogenesis cued by decreasing temperatures and decreasing day length photoperiod. In tropical amphibians that are exposed to fairly constant temperatures and a minimally fluctuating photoperiod, the ovarian cycle may be cued by rainfall, rising or falling barometric pressure, or other environmental cues. In captive situations, a female may not receive the appropriate environmental cues to initiate an ovarian cycle and thus may continue to accumulate fat deposits. This is likely to cause lipids to be present in the circulatory system at unusually high levels for an abnormal period of time. This abnormal physiologic state may result in the inappropriate accumulation of lipids in other tissues. It is also possible that the transport and utilization of fat-soluble vitamins may be impacted by this abnormal lipid metabolism.Captive male anurans are likely to have differences in lipid metabolism from wild specimens. Wild male anurans typically invest a large amount of energy in vocalization or other mate-attracting behaviors. The amount of energy expended by a calling spring peeper (Pseudacris crucifer) is immense. This 5-g frog consumes about 1.51 mL O2/g-h when calling as compared to 0.11 mL O2/g-h during forced exercise [
[3]
]. The vocalization is sustained over the mating season largely by fat depots accumulated the previous year. By the end of the breeding season, a male spring peeper has lost most of its lipid reserves in its coelomic fat bodies, but the reproductive strategy of this species demonstrates that the rate of call production and energy expended for calling is directly tied to breeding success of the male. Thus, the exhausted male is most likely to have successfully courted a mate! Typically the postbreeding fat bodies weigh less than 10% of their prebreeding season weight [[3]
]. In captivity, many anurans are not maintained in a manner that replicates a normal breeding season. Even when attempts are made to induce breeding behavior in captive anurans, the artificial breeding season is much shorter than the natural breeding season. Given the profound difference in oxygen utilization between exercise and breeding vocalization noted in male spring peepers, captive male anurans rarely expend energy at the same rate as they would in the wild. The consistent feeding regimen in captivity produces male anurans that are likely to have a higher percentage of body fat than wild specimens throughout the year.Amphibians are ectotherms and rely on the external environment as a heat sink or source. Unfortunately, the natural temperature cycle a wild anuran may experience is rarely duplicated in the captive environment. For example, wild White's tree frogs, (Pelodryas caerulea), a commonly available species in the pet trade, often bask in the sun and sustain body temperatures in excess of 100°F for several hours. Obviously, this behavior has profound impact on the metabolism of the frogs. Most research and experimental manipulation has focused on homeostasis of water with respect to temperature regulation; unfortunately, there are few studies on the effect of elevated body temperatures on lipid metabolism. Obviously, in an ectotherm a rise in temperature is directly correlated with an increase in metabolism, which may, in turn, cause an amphibian to draw upon its fat reserves to sustain an elevated metabolic rate. Pet tree frogs are commonly maintained in a 10- or 20-gallon aquarium with no external heat source; the thermal gradient is typically between 70 and 80°F, and there is no access to a hot basking spot exceeding 100°F. Because many of the species affected by corneal lipidosis in captivity are also species that bask in the wild (eg, White's tree frog, P. caerulea; Cuban tree frog, Osteopilus septentrionalis), it is possible that an inadequate thermal environment plays a role in the development of the disease. In fact, Shilton et al [
[5]
] did not provide an environmental temperature over 88°F for the Cuban tree frogs used in a study of serum lipids and corneal lipidosis; whether temperature is a contributing factor in the development of corneal lipidosis remains unproven, but repeating this experiment and allowing the subject animals to bask may prove edifying. Although hibernation was mentioned previously specifically for its impact on gonadal development, it is possible that cooling temperatures and subsequent hibernation may be necessary to trigger a natural physiologic change in fat metabolism. If natural thermoregulatory behaviors are denied or truncated in the captive environment, it is likely that lipid transport and storage will be impacted.Many amphibians aestivate during harsh conditions. Sirens, a family of aquatic salamanders, rely heavily on lipid stores to sustain them through aestivation. Captive sirens rarely are subjected to the environmental extremes that induce aestivation (ie, hot dry weather) and do not have the need to expend and then replenish their lipid stores as do wild specimens. Many other aspects of wild amphibian behavior, from foraging to defense of territory, require significant energy, and are altered to a large degree by the captive environment. It is unlikely that most captive environments provide sufficient outlets for the burning and replenishment of fat stores, and as a consequence, the captive amphibian's lipid metabolism is likely to be quite different from a wild specimen.
Amphibians use the typical vertebrate pathways to oxidize lipids [
[6]
]. β-Oxidation burns fatty acids and the tricarboxylic acid cycle oxidizes acetyl-CoA units. Carboxylation of pyruvate or phosphenolpyruvate forms oxaloacetate to balance the drains of the intermediate biosynthetic cycles. Metabolic water is produced during aestivation through the oxidation of triglycerides. However, it is difficult to establish links between lipid metabolism and diet because no comprehensive nutritional analysis has been performed on the diet of wild specimens of any amphibian species, and only a few studies have looked at the actual nutrient composition of an amphibian. One study evaluated the total fatty acid composition of the coelomic fat bodies of a neotenic tiger salamander (Ambystoma tigrinum) along with changes in the free fatty acid levels of the fat bodies during vitellogenesis [[7]
]. Between 96.6% and 99.7% of the fat bodies weight was lipids, either triglycerides, steroids, phospholipids, or free fatty acids. Palmitiric and stearic acids were most abundant, while lauric, myristic, palmitoleic, oleic, linoleic, and arachidic acids were also detected. The relative composition of these fatty acids did not change during vitellogenesis. However, as the fat bodies were depleted, there was a corresponding increase in the levels of free fatty acids. It was suspected that free fatty acids and fatty-acetyl CoA compounds regulate vitellogenesis and possibly other metabolic processes based on work in other vertebrates [[7]
]. A recent study demonstrated a profound correlation between elevated dietary cholesterol and the development of hypercholesterolemia and corneal lipidosis in Cuban tree frogs (O. septentrionalis), but this study did not obtain total fatty acid analysis of either the fat bodies or the whole bodies of the study animals [[5]
]. Without this analytical step, it is difficult to evaluate whether or not there is an abnormal metabolic pathway associated with hypercholesterolemia.Lipids in the diet
The types of lipids ingested by an amphibian are likely to vary significantly based on the lipid profiles of the prey species, and different species of amphibians are likely to have profoundly different feeding strategies, satiety cues, and digestive processes [
[8]
]. Most amphibians feed on hundreds of different species of invertebrates over the course of one year. Because each species of invertebrate has a slightly different nutrient composition than the others, a wild amphibian is likely to have consumed quite different levels of nutrients than what a captive amphibian has consumed by eating a diet composed of the three commonly available “domestic” insects (eg, domestic cricket, fruit fly, mealworm). These prey items have, in turn, been raised on artificial diets, and may have different fat profiles than what would be consumed by “wild” prey. One study documented that the mealworm (Tenebrio molitor) can grow and metamorphose normally on a linoleic acid-free diet [[9]
]. The linoleic acid content of mealworms fed a normal diet was 20%, while that of the deprived mealworms was 10%. Certain insects may therefore have insufficient levels of linoleic acid to support normal amphibian lipid metabolism; however, the impact of varying concentrations of the different free fatty acids is unknown. Given the consistency of relative concentrations of fatty acids during vitellogenesis and their possible role in metabolic regulation, it is likely that a deficient diet will impact the health of an amphibian. Many insects, including domestically cultured insects such as fruit flies (Drosophila melanogaster) and mealworms, require cholesterol in their diet to develop and reproduce normally [[10]
]. They can tolerate higher levels of cholesterol in their daily diet than they would encounter in the wild. Crickets are often raised on commercially produced dog kibble that has significantly higher levels of cholesterol than the diets crickets would consume in the wild. Shilton et al [[5]
] demonstrated that captive Cuban tree frogs (O. septentrionalis) consuming domestic crickets with a dry matter content of 0.5–0.7% cholesterol developed higher serum cholesterol than wild frogs; captive frogs offered a high cholesterol diet (ie, domestic crickets fed a diet to produce a cholesterol content of 1.5% Dry Matter (DM) in the cricket) developed higher serum cholesterol than either the wild frogs or captive frogs fed domestic crickets. Furthermore, VLDL, LDL and HDL cholesterol, as well as cholesterol-phospholipid ratio, were mildly to markedly elevated in the captive frogs compared to wild frogs [[5]
]. It is likely that most captive amphibians consume more cholesterol than they would in the wild. Corneal lipidosis and xanthomatosis, which have been linked to high cholesterol diet and hypercholesterolemia in other species, may result from errors in lipid transport and storage as a result of this high-cholesterol diet.Abnormal lipid metabolism may also impact fat soluble vitamin absorption and distribution. Hypovitaminosis A classically causes keratinizing squamous metaplasia and secondary keratomalacia in mammals and birds (A. Pessier, personal communication, 2001). To date, this lesion has not been described in amphibians. Hypovitaminosis A may cause xerophthalmia as a result of metaplasia of the lacrimal glands or Goblet cells. The corneal lesions also may result from abnormal differentiation of the corneal epithelium due to inadequate levels of vitamin A. Epidermal hyperplasia and hyperkeratosis are also associated with hypovitamonosis A, and these lesions have been seen in Wyoming toads, Bufo baxteri (A. Pessier, personal communication, 2001). Recent work by members of the American Zoo and Aquarium Association's Wyoming Toad Species Survival Plan found lower levels of vitamin A in the livers of captive specimens of this endangered toad compared to free-ranging specimens of this and other toad species (A. Pessier, personal communication, 2002). This data should not be overinterpreted, as only a few liver specimens have been analyzed for vitamin A to date. However, because the diet fed to these toads is similar to diets fed to other anurans in captivity that have not developed signs of hypovitaminosis A, it does suggest that there may be species-specific difference in the requirement of vitamin A for normal epidermal development. Ocular gland metaplasia and lingual squamous metaplasia has been detected in a golden mantella (Mantella aurantiaca), but the small size of this species precluded vitamin A analysis of the liver (A. Pessier, personal communication, 2002).
Corneal lipidosis, xanthomatosis, and hypercholesterolemia
Cuban tree frogs (O. septentrionalis) have been the focus of several publications on corneal lipidosis [
5
, 11
, 12
, 13
]. Since the initial reports, many other amphibian species have been diagnosed with the disease [14
, 15
, 16
, 17
]. Carpenter et al [[11]
] originally described this lipid disorder based on three wild-collected captive Cuban tree frogs as xanthomatous keratitis with disseminated xanthomatosis and atherosclerosis. Although some clinicians prefer the term lipid keratopathy, the term corneal lipidosis became commonly used for this disease after the report by Russell et al [[13]
] of corneal lesions in wild-collected Cuban tree frogs held in captivity for 3 years. Carpenter et al [[11]
] noted a white stromal infiltrate adjacent to the limbus in one frog, but the other two frogs in the report already had significant corneal lipidosis at the time of examination. Initial signs noted by Russell et al [[13]
] were corneal opacities beginning in the limbus that spread over the next 8–20 months to cover 100% of the cornea. The lesions infiltrated the unaffected cornea in a horizontal striate pattern that affected all layers of the cornea as assessed by slit-lamp examination. Typically, the disease progresses as the infiltrate becomes thickened. The surface of the cornea may become raised and irregular, looking remarkably like a dab of lard has been placed on the eye. At this point it is common for the cornea to be heavily vascularized and bleed when touched.At present, few captive amphibians undergo regular serum or plasma biochemical tests as part of a regular health assessment; thus, the data obtained on abnormal frogs may be difficult to interpret properly. Carpenter et al [
[11]
] and Russell et al [[13]
] each obtained serum from two frogs; only the latter study showed unequivocal hypercholesterolemia (see Table 1). Shilton et al [[5]
] fed Cuban tree frogs high-cholesterol diet (1.5% DM) to document when frogs developed hyperlipidemia, hypercholesterolemia, and clinically observed signs of corneal lipidosis or xanthomatosis. In as little as 9 months on a high-cholesterol diet (and 13 months in captivity total), arcus lipoides cornae and concomittant hypercholesterolemia were detected in about half of the frogs yet none of the control frogs were similarly affected [5
, 12
] (see Table 1). Shilton et al [[5]
] demonstrated a significant elevation in circulating cholesterol, including VLDL, LDL, and HDL cholesterol, in control frogs fed a typical captive diet compared to wild frogs. It is reasonable to extrapolate that the majority of captive amphibians may be eating diets excessively high in cholesterol. A typical captive diet may take 36 months or longer to induce the disease on a typical captive diet [[13]
]. Wright and Whitaker [[17]
] reported on corneal lipidosis in other species and often noted plasma or serum cholesterol over 1000 mg/dL for severely affected frogs.Table 1Published serum lipid values for Cuban tree frogs (Osteopilus septentrionalus) with corneal lipidosis
| Cholesterol | Triglycerides | HDL | LDL | VLDL | |
|---|---|---|---|---|---|
| Carpenter et al. (1986) [11] | 196–201 mg/dL n = 2 | 84–94 mg/dL n = 2 | 22–25 mg/dL n = 2 | 62–65 mg/dL n = 2 | N/A n = 2 |
| Russell et al. (1990) [13] | 683–791 mg/dL n = 2 | 47–86 mg/dL n = 2 | 80 mg/dL n = 1 | 702 mg/dL n = 1 | 9 mg/dL n = 1 |
| Keller et al. (2000) [12] Note that these are preliminary results of an experiment reported Shilton et al. (2001). [5] There are some discrepancies between the sources. | Affecteds 27.3±19.8 mmol/L (∼1050 mmol/dL) n = 16 | N/A | N/A | Affecteds 17.8±18.9 mmol/L n = 16 | N/A |
| Controls 16.5±20.4 mmol/L (∼635 mg/dL) n = 17 | Controls 9.0±7.6 mmol/L n = 17 | ||||
| Wild 3.1±2.1 mmol/L in females, 5.3±2.6 mmol/L in males) (∼118 mg/dL) n = 17 | |||||
| Shilton et al. (2001) [5] | |||||
| High-cholesterol diet | |||||
| Female | 34.1±15.2 mmol/L n = 15 | 1.2±0.9 mmol/L n = 15 | 2.6±0.6 mmol/L n = 5 | 16.8±6.8 mmol/L n = 5 | 21.8±13.1 mmol/L n = 5 |
| Male | 22.8±14.8 mmol/L n = 6 | 0.6±0.2 mmol/L n = 6 | 2.7±0.3 mmol/L n = 4 | 2.7±0.3 mmol/L n = 5 | 3.4±3.3 mmol/L n = 4 |
| Regular diet | |||||
| Female | 12.3±8.7 mmol/L n = 21 | 1.1±0.9 mmol/L n = 21 | 1.5±0.4 mmol/L n = 7 | 8.7±5.4 mmol/L n = 7 | 2.4±2.8 mmol/L n = 7 |
| Male | 10.3±3.1 mmol/L n = 5 | 0.5±0.3 mmol/L n = 5 | 2.2±0.5 mmol/L n = 4 | 7.3±2.3 mmol/L n = 4 | 0.5±0.2 mmol/L n = 4 |
| Wild | |||||
| Female | 3.1±2.1 mmol/L n = 19 | 0.4±0.4 mmol/L n = 19 | 0.9±0.4 mmol/L n = 15 | 2.1±1.6 mmol/L n = 15 | 0.1±0.1 mmol/L n = 5 |
| Male | 5.3±2.6 mmol/L n = 10 | 0.4±0.3 mmol/L n = 10 | 1.3±0.5 mmol/L n = 6 | 3.0±1.7 mmol/L n = 6 | 0.3±0.2 mmol/L n = 6 |
Carpenter et al [
[11]
] noted disseminated xanthomatosis in one Cuban tree frog. Xanthomas were noted in the cornea and sclera, subcutaneously (especially over extensor surfaces), peripheral nerves, ovaries, lungs, stomach, pituitary, and brain. Atherosclerosis of the aorta and femoral arteries was noted. The liver and spleen were heavily infiltrated with fat but did not have xanthomas. About 50% of the liver mass was determined to be composed of neutral fats. Extracellular and intracellular cholesterol crystals were confirmed by polarization and neutral lipids were confirmed with oil-red-O stains. Macrophages, multinucleated giant cells and lymphocytic infiltrates comprised the inflammatory response along with melanocytes and mast cells. Russell et al [[13]
] described the corneal lesions as severe xanthomatous lesions consisting of cholesterol clefts, granuloma formation adjacent to Descemet's membrane, and mineralization adjacent to Bowman's membrane. The granulomatous cellular response consisted primarily of macrophages and lymphocytes. Xanthomas were detected in the central and peripheral nervous system, the skin and the kidneys. Russell et al [[13]
] proposed that the pattern of progress of the corneal lesion suggested infiltration via the corneal nerve due to the presence of xanthomas in the central nervous system. Shilton et al [[5]
] did induce corneal lipid deposition, termed corneal arcus, but did not detect xanthomas in any experimental or control animals. Atherosclerosis, a lesion commonly associated with hypercholesterolemia in mammals, has been detected in frogs with xanthomatosis [[11]
], although this lesion was not detected by Shilton et al [[5]
].Carpenter et al [
[11]
] and Russell [[13]
] cite vitamin A as an initial treatment when the corneal lesions were detected, but neither provide a rationale for the treatment. Hypovitaminosis A may cause abnormal epithelial differentiation and cornification of the cornea; abnormal epithelial cells may die or otherwise cause inflammation and a granulomatous response, which then evokes cholesterol accumulation in the surrounding tissues. It is also possible that the abnormal epithelia first may create extracellular deposits of cholesterol that subsequently trigger the granulomatous response. Species that have been documented with corneal lipidosis may have insufficient vitamin A in their diets, and thus their fat-soluble vitamin profiles should be reassessed. Unfortunately, by the time clinical signs of corneal lipidosis are detected, treatment with vitamin A is unlikely to be effective or palliative.Prevention and treatment of cholesterol-related disorders
Diagnosis of cholesterol-related disorders relies principally on observation of corneal lesions and concomitant confirmation of elevated serum or plasma cholesterol. Adjunct diagnostics should include celioscopy or an exploratory celiotomy to evaluate the extent of lipidosis and xanthomatosis. A liver biopsy should be obtained as well as biopsies from any grossly visible lesions. The clinician must be aware that other granulomatous diseases, such as mycobacteriosis and chromomycosis, may appear grossly similar to xanthomatosis. A touch-prep of biopsy material should be evaluated by acid-fast stain and Gram stain to rule out these infectious etiologies. If disseminated xanthomatosis is detected or if hepatic lipidosis is confirmed, the amphibian is unlikely to survive more than 9–12 months in my experience.
Surgical removal of one or both coelomic fat bodies may be warranted. Although extracellular cholesterol may be difficult to mobilize, these and other lipid depots may be metabolized if the main lipid storage organs are removed. An amphibian may have a reduced capability to deal with sudden increases in energy or lipid requirements after the coelomic fat bodies have been excised. These patients require care to maintain adequate nutritional intake and stable weights. Debulking of corneal xanthomas may provoke more inflammation and speed the infiltration of the perimeter tissue, but may be necessary when the infiltrates become very thick. Enucleation may be considered for severely infiltrated eyes as a pain-management procedure.
Treatment of corneal lipidosis is unrewarding, as there is likely to be concurrent systemic xanthomas affecting organ function and concomitant hepatic lipidosis. Even if eye lesions are minimal, internal pathology may be severe, and the reverse may be true. However, affected amphibians may survive years with proper management. Careful weight control is necessary so that the amphibian does not continue to convert excess energy to lipids. This point should be reemphasized, as most captive amphibians are fed a far higher calorie load than they require. For example, a 50-g White's tree frog (P. caerulea) maintained at 25°C requires around 0.54 kcal/day for basic metabolism, a caloric intake of approximately six adult domestic crickets per week [
[17]
]. I observe that most pet owners feed their White's tree frogs at least two to three times this amount of food on a weekly basis. I recommend feeding affected amphibians no more than once a week, and then to feed them sparingly at that time. Diet should be modified to reduce the level of ingested cholesterol. This may be accomplished by using wild-caught insects and earthworms as a major portion of the diet. Reduce the amount of domestic crickets and mealworms fed to the affected amphibian. If you do use domestic crickets or mealworms, I recommend feeding the insects solely vegetables for at least 48 hours beforehand so they fully defecate the previous diet they consumed; do not feed the insects dog food or any other diet with added cholesterol! I have maintained three moderately affected White's tree frogs on this regimen for over a year without seeing significant expansion of the corneal lesions. Creating an appropriate thermal environment is an essential aspect of treatment. Basking spots should be provided around the clock, ranging to 85°F in temperate species and 105°F in tropical species, with background temperatures of 15–30°F lower. Topical antibiotic and antiinflammatory drops may be needed to control inflammation. Gentamicin ophthalmic solution and cortisone-based ophthalmic solutions may be administered three to six times a day as needed. Systemic antiinflammatories and analgesiacs may also be useful for pain management (eg, flunixine meglumine 1 mg/kg intracoelomicly q 24h). All amphibians with corneal lipidosis, xanthomatosis, or hypercholesterolemia should have their plasma or serum analyzed periodically to determine if there is any change in circulating cholesterol.Most amphibians die within 18–24 months of diagnosis, although some frogs survived well over 48 months. However, the quality of life for blind frogs is certainly an ethical issue. Tree frogs especially are highly visual animals—they rely on vision for recognizing their home, detecting food, finding basking sites, and avoiding predators. Once blind, tree frogs typically remain in one spot and do not attempt to thermoregulate. It is likely that the demands of thermoregulation and eating are outweighed by predator avoidance behavior. They continue to feed as prey items bump into them or they may learn to hand feed from their caregiver. My current opinion is that a blind tree frog does not have a high quality of life, and is likely to be under considerable stress. Furthermore, based on human reports of corneal xanthomas, this is a painful disease. Euthanasia should be discussed at the time of diagnosis and an understanding reached with the caregiver as to what constitutes a crisis point beyond which an amphibian should be euthanized.
There are many unanswered questions concerning amphibian lipid metabolism and disorders. It appears that the captive diet is much higher in cholesterol than wild diet of amphibians. Is there a way to provide a lower cholesterol diet using the “domesticated” insects? Are there alternative prey sources with lower cholesterol that can be used as a primary diet? Are any of the cholesterol-lowering drugs prescribed for humans efficacious in amphibians? What role does hypovitaminosis A play in this disease? Is injury a primary cause of inflammation leading to corneal lipidosis, or is cholesterol deposition the inciting cause of the inflammatory process? Future directions for research should focus on the lipid composition of captive and wild diets, whole body and serum lipid composition of healthy wild amphibians and affected captive specimens, the hepatic vitamin A content of wild and captive amphibians, and documentation of the pathology of hypovitaminosis A in amphibians.
Summary
Many captive amphibians have high serum or plasma cholesterol and concomittant lesions such as corneal lipidosis and xanthomas. The underlying cause of this disorder is unknown, but it is likely that a diet high in cholesterol plays a role. The metabolism of lipids in healthy amphibians remains poorly documented, which makes it challenging to interpret the findings in affected specimens. Affected amphibians should be maintained on a low-cholesterol diet and fed sparingly, and their captive environment modified to provide an optimal temperature gradient for thermoregulation.
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© 2003 Elsevier Science (USA). Published by Elsevier Inc. All rights reserved.
