Light-Induced Photoreceptor Degeneration in the Mouse Involves Activation of the Small GTPase Rac1

Abstract

Rac1 may play a role in the apoptosis of light-damaged photoreceptors. The increased expression of PAK4 after light stimulus possibly functions as a protective mechanism against apoptosis.

Depleting Rac1 in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function

“…Excessive bright light exposure leads to rhodopsin-mediated stimulation of apoptotic cell death of rod photoreceptors in several species, including mouse (21). Rac1 is a potent proapoptotic factor (16), and is activated in mammalian retinas in response to light (10,11). We explored a role for Rac1 in light-induced photoreceptor apoptosis by exposing mice to 15,000 lux illumination for 24 h and evaluating rod survival 7 d later.…”

“…Rac1 expression has been reported in mammalian rod photoreceptors based on immunohistochemistry, but the expression pattern of Rac1 in rods is still under debate (9)(10)(11). Rac1 is activated in response to light stimuli in the mammalian retina (10,11), but the specific role of Rac1 in mammalian photoreceptors remains to be elucidated.…”

Immunohistochemical characterization of the chick marginal retina

“…In addition to anti-calbindin, fluorescently labeled peanut agglutinin (PNA; Vector Laboratories, FL-1071 at 1:50 dilution) was also used as a cone-specific marker (14,15).…”

Crumbs limits oxidase-dependent signaling to maintain epithelial integrity and prevent photoreceptor cell death

“…In epithelial cells, Crbdependent inhibition of Rac1 limits NADPH oxidase and PI3K activation to preserve epithelial tissue integrity (this study and Chartier et al, 2011). In retinas, loss of the inhibitory action of Crb coupled to light, a known activator of Rac1 (Balasubramanian and Slepak, 2003;Belmonte et al, 2006), results in ROS accumulation and photoreceptor cell death. Thereby, our study contributes to illuminate the molecular mechanisms regulating epithelial polarity, a crucial aspect of epithelial tissue morphogenesis and physiology in most organs.…”

“…Indeed, Rac1 operates downstream of Rhodopsin in Drosophila and mammals (Chang and Ready, 2000;Balasubramanian and Slepak, 2003). Consequently, Rac1 is activated by light (Balasubramanian and Slepak, 2003;Belmonte et al, 2006), which triggers relapse of crb mutant retinas (Johnson et al, 2002). Thus, it is plausible that Crb fulfills a protective role during light exposure by limiting Rac1-NADPH oxidase complex activity and oxidative damage downstream of light-activated Rhodopsin.…”