JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
Signalment (JPC # 2640635): Salt water, penned Atlantic salmon (Salmo salar), first and second year stock
HISTORY: Over the course of several months, 6-16% of the stock of 100,000 fish developed lenticular cataracts. The fish were intensively farmed and maintained on a low grade, producer formulated ration.
HISTOPATHOLOGIC DESCRIPTION: Eye, lens: Multifocally, separating and replacing subcapsular lens fibers are variably sized, irregularly shaped eosinophilic homogeneous to granular globules (morgagnian globules). Multifocally individual lens epithelial cells deep to the superficial lens epithelium, are markedly hypertrophied with abundant eosinophilic microvacuolated cytoplasm and retained nuclei (bladder cells).Lens epithelium, especially at the poles of the lens, is hyperplastic forming up to 3 cell layers. At one pole, lens epithelial cells become spindyloid and are separated by fine collagen fibers (fibrous metaplasia). There are multifocal large lakes of proteinaceous fluid replacing lens fibers (liquefied lens fibers).
MORPHOLOGIC DIAGNOSIS: Eye, lens: Cataractous change, circumferential, moderate to severe, with epithelial hyperplasia, posterior lens epithelial migration, and fibrous metaplasia, Atlantic salmon (Salmo salar), piscine.
ETIOLOGIC DIAGNOSIS: Nutritionally induced cataract
- Cataract, the most common and important disorder of the lens, is a permanent opacity resulting from increased hydration of the lens due to alterations in nutrition, metabolism, or osmotic balance of the lens
- Three major categories in veterinary practice:
- Inherited, postinflammatory, idiopathic
- Lens: transparent, cellular, but avascular structure
- Surrounded by a basement membrane (lens capsule)
- Composed of approximately 65% water, and 35% protein
- Transparency maintained by several factors including low cytoplasmic density (i.e. lack of intracellular organelles), spatial fluctuations of refractive index of cytoplasm and highly organized lattice arrangement of fiber cells
- Protein component is approximately 90% soluble protein (crystallins) within the cytoplasm and 10% insoluble protein (albuminoid) within the cell membranes and nucleus
- Beneath the lens capsule is a layer of epithelial cells that, at the equator, proliferate and elongate, forming the prismatic lenticular fibers that lose their nucleus and become compacted into the oldest central part of the lens (nucleus)
- Glucose, present in the aqueous humor, is the major energy source for the lens
- Cataract may form secondary to diabetes mellitus, glaucoma, inflammation, developmental anomalies in the anterior chamber, physical and chemical insults (e.g. solar or irradiation, cold, increased intraocular pressure, inflammation, trauma, and nutritional excesses or deficiencies).
- Although the pathogenesis is often difficult to determine, the common link is the imbalance between the substrate supply and enzymatic activity within the anaerobic lens
- General pathogenesis: degradation of capsular epithelium > loss of Na-K-dependent ATPase osmotic pumps (increased Na and Ca levels/decreased K, oxygen consumption and ATP production) > loss of normal lens hydration status > lens fiber proteins become denatured (increased hydrolytic and proteolytic enzyme activity) > accumulation of smaller peptides > osmotic fluid imbibitions
- Diabetic cataract
- Usually bilateral; develop in about 70% of spontaneously diabetic dogs
- Opacity begins in the cortex at the equator and progresses to complete opacity within a few weeks
- Diabetic cataract pathogenesis:
- High glucose in aqueous > hexokinase overwhelmed > shunted to sorbitol pathway (glucose to sorbitol by aldose reductase)> sorbitol accumulates > osmotic movement of water into lens > hydropic cell rupture
- Hexokinase is the rate limiting enzymatic step; reduction of sorbitol to D-fructose is much slower, thus sorbitol accumulates
- Oxidative damage is also thought to play a role
TYPICAL CLINICAL AND GROSS FINDINGS:
- Partial to complete blindness
- Opaque lens
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Definitive histologic changes by importance: Morgagnian globules > bladder cells > lens epithelial hyperplasia > posterior migration of lens epithelium > mineralization
- Lenticular epithelial changes
- Epithelial hyperplasia
- Fibrous metaplasia: Forms a multilayer plaque along the capsule
- Posterior subcapsular epithelial cell migration
- Bladder cell formation: Epithelial cells/lens fibers become swollen and balloon-like with retained nuclei
- May have a paucity or absence of epithelial cells
- Lenticular fiber changes
- Fragmentation or liquefaction of lens fibers
- Proteinaceous fluid from lytic denatured lens proteins accumulates between lenticular fibers forming clefts, vacuoles, lakes, and eosinophilic extracellular globules (Morgagnian globules)
- Calcium salt deposition and mineralization
- Aggregation of cytoplasmic proteins results in increased staining intensity
- Cataracts in farmed fish:
- Sunlight induced: The lens absorbs most of the harmful rays that would damage the retina
- Trematode larva infestation Diplostomum (formerly Diphostomum sp)
- Dietary amino acid, zinc, Vit C, or histidine deficiency
- Nuclear or lenticular sclerosis in dogs
- Common in dogs older than 7 years and occurs from progressive lens fiber formation and internal compression of older lens fibers at the nucleus
- Whitish-blue appearance to the lens with retention of tapetal or fundic reflection
- Characterized microscopically by loss of concentric laminations
- Differentiation between early nuclear cataract and dense nuclear sclerosis is often difficult
- Soemmering ring cataract: Circumferential ring of lens fibers that grow from lens epithelium that has been left behind during cataract surgery, in which there has been removal of degenerate lens material and implantation of an artificial lens
- Bovine: Congenital cataract can result from in utero infection with bovine viral diarrhea virus (Pestivirus)
- Cats: Diabetes mellitus usually develops in older cats (> 7years); older cats have lower levels of aldose reductase, therefore rarely develop diabetic cataracts; young cats have a higher level of aldose reductase and can develop cataracts
- Dogs: puppies, wolf cubs and kittens fed commercial milk replacer can get cataracts due to arginine deficiency
- Dogs, humans: Hypocalcemia
- Common in renal failure or primary or secondary hypoparathyroidism
- Hypocalcemia > disruption of Na-K-dependent active transport of sodium out of the lens > osmotic fluid imbibition
- Characteristic multifocal, punctate opacities or bilaterally symmetrical coalescing lamellar cortical opacities
- Kangaroos, wallabies: Galactose-induced cataracts
- Orphaned kangaroos and wallabies raised on cows’ milk (higher in lactose)
- Thought to be similar pathogenesis as diabetic cataract except rather than glucose/sorbitol, galactose/dulcitol
- Mice: NOD mice selectively bred for cataracts
- Rabbit: Encephalitozoon cuniculi infection in dwarf rabbits causes uveitis, cataracts, phacoclastic uveitis
- Autosomal recessive genetic disorder of New Zealand White rabbits
- Rats: albino rats exposed to light levels of 130 lux or higher at cage level
- Sows: Aminoglycoside antibiotics and anthelmintic hygromycin B induce posterior cortical and subcapsular cataracts
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- Richter M, Guscetti F, Spiess B. Aldose reductase activity and glucose-related opacities in incubated lenses from dogs and cats. Amer J Vet Res 2002;63(11):1591-97.
- Waagbø R, Troße C, Koppe W, Fontanillas R, Breck O. Dietary histidine supplementation prevents cataract development in adult Atlantic salmon, Salmo salar, in seawater. British Journal of Nutrition 2010;104:1460–1470.
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