98th Annual Meeting DOG 2000

R 439

Rod photoreceptors neuroprotection increases cone survival in an animal model of inherited retinal degeneration

J. A. Sahel, S. Mohand-Said, M. Frasson, T. Léveillard, S. Picaud, D. Hicks, H. Dreyfus

Purpose : The rod-cone retinal degenerations (Retinitis Pigmentosa) are typified by initial loss of rod photoreceptors followed by secondary cone photoreceptor death. In most cases, rod death is due to gene mutations expressed specifically in these cells, leading to scotopic vision loss. We showed earlier, using both in vivo (Mohand-Said et al, 1998) and in vitro (Mohand-Said et al, 2000) approaches that cone survival is dependent on rods. The current studies were initiated in order to determine whether protection of rods allowed an increase in cone survival.

Methods : C3H mice carrying the rd mutation were treated with subretinal injections of glial cell line derived neurotrophic factor (GDNF), and gene directed pharmacological blockers (e.g. calcium channel antagonists). The effect on photoreceptor survival was assessed by cell counting on flat mounted retinas using an unbiased stereological approach and on histological sections. Cone function was evaluated using electroretinography.

Results : Both the neurotrophic and gene directed pharmacological strategies were effective in rescuing rods in this model (on average 30% rescue). Moreover cone numbers and function were significantly increased in treated animals. These data further support the hypothesis that cone survival depends on rods.

Conclusions: As cone cells are responsible for high acuity and colour vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to understanding underlying interactions between retinal photoreceptors.

Clinique Ophtalmologique and Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine. Inserm/Université Louis Pasteur, F-9918, Strasbourg, France