Complement Deposition and Microglial Activation in the Outer Retina in Light-Induced Retinopathy: Inhibition by a 5-HT_1AAgonist

Abstract

In blue light exposed retinas, microglia were activated and migrated toward the outer retina, whereas a T-lymphocyte response was minimal. The innate immune system was markedly activated, with substantial complement deposition in the outer retina after light exposure. This complement deposition was prevented by AL-8309A. This model may be useful in the evaluation of complement inhibitors and other neuroprotectants intended for ocular use. AL-8309 is under evaluation in the clinic and may be useful in the treatment of AMD.

Detection of Complement Activators in Immune Attack Eyes After iPS-Derived Retinal Pigment Epithelial Cell Transplantation

“…In animal AMD models, Collier et al 26 reported that administration of a 5-HT 1A agonist (AL-8309A) prevented retinal lesions and decreased the activation of retinal microglia and complement deposition in the retina after light exposure. Therapies that are currently in clinical trials for AMD patients include complement inhibitors such as ARC1905 (target ¼ C5), FCFD4514S (target ¼ Factor D), and POT-4 (target ¼ C3).…”

Fundus Camera-Delivered Light-Induced Retinal Degeneration in Mice With the RPE65 Leu450Met Variant is Associated With Oxidative Stress and Apoptosis

“…Hypoxia, hypoxia inducible factors, and erythropoietin, 37–39 halothane anesthesia, 40 complement inhibition (CFD KO mice), 17 iron chelation, 20 dexamethasone, 41 and free-radical scavengers 42 all can lead to decreased light injury. On the other hand, blue light may increase light injury 43 by promoting the regeneration of rhodopsin. 44 One proposed pathway for light-induced apoptosis starts by absorption of light energy by rhodopsin.…”

Neuroprotective actions of progesterone in an in vivo model of retinitis pigmentosa

“…The recruitment of glia to damaged regions occurs in almost every pathological condition in the CNS and in a range of retinal pathologies, including age-related macular degeneration, RP, late-onset retinal degeneration, retinal detachment, glaucoma, diabetic retinopathy and in many experimental models of retinal degeneration [49][50][51][52][53][54][55][56][57]. The most well known aspect of the glial response in the retina is that Müller cells upregulate GFAP, a protein considered to be a marker for reactive gliosis, not only in the retina, but also across the entire CNS [58].…”