Prevention of photoreceptor cell degeneration following retinal detachment in BAX-deficient mice

Abstract

Retinal detachment (RD) is a leading cause of blindness in young adults. To seek a better understanding of the mechanisms underlying photoreceptor cell loss following RD by taking advantages of the technology of mouse genetic engineering, we developed an experimental RD model in mice. Retinal detachment was created in adult mice by subretinal injection of 1.4% sodium hyaluronate. Following 1, 3, 7, and 28 days post-operation, mouse retinal sections were subjected to histochemistry, terminal doexynucleotidyl transferase dUTP nick-end labeling (TUNEL), and immunofluorescence microscopy. To study the mechanisms underlying photoreceptor degeneration, we compared retinal cell death in wild-type and Bax-deficient mice. In consistent with that reported in the other animal models, TUNEL-positive cells were found only in the outer nuclear layer of the detached portion of the retina. The number of TUNEL-positive cells peaked on day 3 following the induction of RD and declined sharply thereafter. After day 7, few TUNEL-positive cells were detected, and the total number of photoreceptor cells remained constant. In addition, we show that both types of photoreceptor cells, rods and cones, followed a similar pattern of cell loss and apoptosis. In contrast, Bax deficiency blocked completely cell apoptosis and photoreceptor degeneration following RD. Therefore, our data support that apoptosis is a key phenomenon leading to photoreceptor dysfunction of RD. Blockage of the activity of the pro-apoptotic molecule, Bax, in a knockout mouse model abolishes completely photoreceptor cell loss and thus may prove to be effective in preventing or treating RD-induced photoreceptor degeneration.