Purpose: Mutations in the photoreceptor cell-specific gene encoding aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) lead to Leber congenital amaurosis (LCA4), retinitis pigmentosa, and cone-rod dystrophy. Gene therapy appears to be promising in the treatment for AIPL1-mediated vision loss in humans. Prior to initiating these treatments, however, it is crucial to understand how the retinal neurons remodel themselves in response to photoreceptor cell degeneration. In this study, using an animal model for AIPL1-LCA, Aipl1(-/-) mice, we investigate the changes in postreceptoral retinal neurons during the course of photoreceptor cell loss.
Methods: Morphology of the Aipl1(-/-) retina from postnatal day 8 to 150 was compared to that of age-matched, wild-type C57Bl6/J retina (WT) by immunocytochemistry using cell-specific markers.
Results: Expression of postsynaptic proteins in bipolar cells is reduced prior to photoreceptor cell degeneration at postnatal day 8. Bipolar and horizontal cells retract their dendrites. Cell bodies and axons of bipolar and horizontal cells are disorganized during the course of degeneration. Müller cell processes become hypertrophic and form a dense fibrotic layer outside the inner nuclear layer.
Conclusions: An early defect in photoreceptor cells in the AIPL1-LCA mouse model affects the expression of postsynaptic markers, suggesting abnormal development of bipolar synapses. Once degeneration of photoreceptor cells is initiated, remodeling of retinal neurons in the Aipl1(-/-) animal is rapid.
Keywords: LCA; childhood blindness; photoreceptor degeneration; remodeling; retina.
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.