Novel immunodeficient Pde6b rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration

Abstract

Retinitis pigmentosa (RP) is a common retinal degeneration disease caused by mutation in any gene of the photo transduction cascade and results in photoreceptor dystrophy. Over decades, several animal models have been used to address the need for elucidation of effective therapeutics and factors regulating retinal degeneration to prohibit or renew the damaged retina. However, controversies over immune privilege of retina during cell transplantation and role of immune modulation during RP still remain largely uninvestigated due to lack of proper animal models. Therefore, in our present study, we have developed an immune compromised mouse model NOD.SCID- rd1 for retinitis pigmentosa (RP) by crossing CBA/J and NOD SCID mice and selecting homozygous double mutant animals for further breeding. Characterization of the newly developed RP model indicates similar retinal degeneration pattern as CBA/J with decreased apoptosis rate and rhodopsin loss. It also exhibits loss of T cells, B cells and NK cells. NOD.SCID- rd1model is extremely useful for xenogenic cell based therapeutics as indicated by higher cell integration capacity post transplantation. The dissection of underlying role of immune system in the progression of RP and effect of immune deficiency on immune privilege of eye has also been further elucidated using comparative qPCR studies of this model with immune competent RP model.