Currently no animal models fully embody exfoliation syndrome (XFS) or exfoliation

Currently no animal models fully embody exfoliation syndrome (XFS) or exfoliation glaucoma (XFG). susceptibility and progression to exfoliation glaucoma (XFG). It is obvious that XFS is definitely a complex age-related disease affected by both genetic and environmental factors. However both the genetic and environmental factors need better definition. 1-4 A strong association between single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (are very common in unaffected settings and the mechanisms of action of these alleles are not obvious. 7 23 Risk alleles at contactin-associated protein-like 2 (cause neurologic disease and it is not clear if allelic genetic background or additional variations modulate the phenotypic effects of mutation with this gene. A host of environmental factors have been suggested to influence XFS but findings are often inconsistent across studies.3 4 The challenge of modeling XFS/XFG To understand the molecular mechanisms underlying XFS and progression to XFG tractable animal models are needed. Extremely NSC 23766 few NSC 23766 publications have studied animal models NSC 23766 of XFS and to our knowledge only 2 animal models have been reported. 27 28 You will find no reports of models with all of the features of XFS with XFG. The lack of animal models has been suggested to reflect the typical event of XFS at aged ages with the belief that model varieties do not live very long enough to develop the condition. Although possible we do not feel that the shorter life-span of model varieties in complete years prevents Rabbit polyclonal to ZNF317. development of XFS. Disease susceptibility in model varieties increases with age relative to life-span in a similar fashion to that in people. 29 For example within a 2 years life span NSC 23766 mice often develop complex age-related diseases that occur later on in human being life. On the other hand variations NSC 23766 in environment may be crucial and profoundly effect whether or not model varieties develop XFS. The degree and nature of exposure to light (UV) low heat viruses and caffeine have all been suggested to impact development of XFS. 4 30 Most laboratory animals are housed in cages with limited UV exposure constant controlled heat limited or no exposure to pathogens and lack of caffeine and additional lifestyle factors. Genetic variations across varieties may also be important. In humans a high-risk genotype in the locus is typically necessary for manifestation of XFS as high-risk alleles are present in almost all individuals with XFS. 23 Therefore the challenge of modeling XFS/XFG in animals is to develop models reflecting these complex genetic and environmental risk factors. Current Models Porcine model The 1st animal model was reported in pigs. 27 The authors fed pigs a high sucrose high salt diet to induce cataracts. They reasoned that cataracts are common in XFS and that mature cataracts shed exfoliative material. After a few months on the diet the pigs developed NSC 23766 cataracts and experienced an exfoliation-like material that contained crystallins. We are not aware of any follow up studies. The relevance of this model to the human being disease is not yet obvious though it may extreme caution against high salt and sugars intakes. mutant mouse model The additional model is an inherited mouse model which shares several features with human being XFS. In addition to the build up of fibrillar material in the eye individuals with XFS have characteristic saw-tooth morphology of the iris pigment epithelium. 34 35 This results in iris transillumination problems characterized by a specific concentric circular transillumination pattern. 36 Much like human being individuals mutant mice have microscopically detectable deposits of fibrillin 1 positive material in the eye. 28 They also replicate the saw-tooth morphology of the iris pigment epithelium and have the same pattern of transillumination problems as human being individuals (Number 1). In human being XFS improved susceptibility to oxidative stress has been suggested to contribute to the pathology 37 38 and as in additional glaucomas levels of transforming growth element beta (TGF-β) superfamily users are elevated 39-42. The mutant iris disease entails oxidative damage 43 and TGF-β levels in mutant eyes remain to be tested. Therefore the mice have some XFS-like phenotypes but lack.