Regulation of Eye Size by the Retinal Basement Membrane and Vitreous Body

Abstract

Congenital high myopia is an early-onset enlargement of the eye globes that carries a high risk for retinal detachment. The genetic basis for congenital high myopia has frequently been connected to mutations in genes encoding extracellular matrix proteins of the vitreous body (VB) and the inner limiting membrane (ILM). Why defective or missing VB and ILM proteins lead to an increase in eye size is unknown. The present study introduces the chick embryo as a model to study the role of ILM and VB in regulating eye size. The ILM and VB were disrupted by injecting collagenase into the eyes of E5 chick embryos. The digestion of VB and ILM proteins was monitored by Western blot and immunocytochemistry. Eye size was assessed up to 9 days after the enzyme injections. Intraocular injection of collagenase led to the disruption of the ILM and the VB by digesting their collagen constituents. Once disrupted, the ILM and the collagen II fibrillar network failed to regenerate despite continued synthesis of VB and ILM proteins. ILM and VB disruption resulted in eye enlargement of 50% within 4 days. The increase in eye size was greatly reduced by reconstituting the ILM. The present data show that the ILM and the VB play major roles in the early regulation of eye size. The authors speculate that the integrity of the vitreoretinal border is an important factor in preventing congenital high myopia.