Gene Transfer Of Bdnf Promotes Cone Survival And Function In A Model Of Retinitis Pigmentosa (RP)

Abstract

Purpose: : To test the effects of increased expression of BDNF on cone survival in a mouse model of retinitis pigmentosa (RP).

Methods: : Rd10^+/+ or rd10^-/- mice in a C57BL/6 background were given a subretinal injection of 5e8 vp of scAAV5-BDNF, scAAV8-BDNF, or vehicle at postnatal day (P) 14. Fourteen days after injection, the levels of Bdnf mRNA were measured in eye cups by real time RT-PCR. At P50, photopic electroretinography (ERG) was done and then mice were euthanized and cone cell density was measured by image analysis of confocal microscopic images of retinal flat mounts stained with rhodamine-labeled peanut agglutinin (PNA).

Results: : Compared to eyecups from eyes injected with vehicle, those from eyes injected with scAAV5-BDNF or scAAV8-BDNF showed a 13.5 and 8.5-fold increase in Bdnf mRNA. At P50, mean (±SEM) photopic b-wave amplitude was 24.4±2.7 µV in eyes of rd10^+/+ mice injected with scAAV5-BDNF compared to 16.5±1.2 µV in eyes of no treatment controls (p=0.01). Cone density was 126.3±10.0 in eyes of rd10^+/+ mice injected with scAAV5-BDNF compared to 92.7±7.8 in no treatment controls (p=0.01).

Conclusions: : Gene transfer of Bdnf by subretinal injection of scAAV5-BDNF promotes cone survival and function in a model of RP.

Keywords: gene transfer/gene therapy • retinal degenerations: hereditary • neuroprotection