Microglial response to light‐induced photoreceptor degeneration in the mouse retina

Abstract

The microglial response elicited by degeneration of retinal photoreceptor cells was characterized in BALB/c mice exposed to bright light for 7 hours and then kept in complete darkness for survival times ranging from 0 hours to 10 days. Photodegeneration resulted in extensive cell death in the retina, mainly in the outer nuclear layer (ONL), where the photoreceptor nuclei are located. Specific immunolabeling of microglial cells with anti-CD11b, anti-CD45, anti-F4/80, anti-SRA, and anti-CD68 antibodies revealed that microglial cells were activated in light-exposed retinas. They migrated to the ONL, changed their morphology, becoming rounded cells with short and thick processes, and, finally, showed immunophenotypic changes. Specifically, retinal microglia began to strongly express antigens recognized by anti-CD11b, anti-CD45, and anti-F4/80, coincident with cell degeneration. In contrast, upregulation of the antigen recognized by anti-SRA was not detected by immunocytochemistry until 6 hours after light exposure. Differences were also observed at 10 days after light exposure: CD11b, CD45, and F4/80 continued to be strongly expressed in retinal microglia, whereas the expression of CD68 and SRA had decreased to near-normal values. Therefore, microglia did not return to their original state after photodegeneration and continued to show a degree of activation. The accumulation of activated microglial cells in affected regions simultaneously with photoreceptor degeneration suggests that they play some role in photodegeneration.

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

“…8). Although this has never before been documented in the rd10 retina, it is not surprising considering a similar response of microglia has been observed in other models of photoreceptor degeneration and insult (Harada et al, 2002;Noailles et al, 2014;Roque et al, 1996;Santos et al, 2010;Thanos 1992;Wang et al, 2014). In the rd mouse model of RP, microglial activation also preceded photoreceptor loss (Zeng et al, 2005) and microglia appeared to migrate from the RGC layer to the ONL, possibly in response to chemokine production by the diseased photoreceptors (Zeng et al, 2005).…”

Light-induced degeneration and microglial response in the retina of an epibenthonic pigmented teleost: age-dependent photoreceptor susceptibility to cell death

“…number of apoptotic nuclei, Müller glial cells or microglial cells per square millimetre (anmm -2 , mgcmm -2 and mcmm -2 , respectively). Similar procedures have been described in the literature (Cook et al, 1998;Mayordomo et al, 2003;Francisco-Morcillo et al, 2004;Santos et al, 2010). Statistical analyses were performed using Student's two-tailed t-test.…”

“…Additionally, it has been demonstrated that rod-dominated retinas, such as in nocturnal rodents, are damaged by forced exposure to moderate light (Wenzel et al, 2005;Santos et al, 2010). Therefore, pure-rod retinas could be more susceptible to damage than cone-rich retinas.…”

“…The rod-dominated retinas of albino strains of rodents and the cone-diurnal retina of albino fish (Teleostei) are damaged by forced exposures to moderate light and this has led to their choice as animal models for the study of light damage to the human retina (Remé et al, 1998;Vihtelic and Hyde, 2000;Allison et al, 2006;Vihtelic et al, 2006;Bernardos et al, 2007;Fimbel et al, 2007;Kassen et al, 2007;Thummel et al, 2008a;Thummel et al, 2008b;Santos et al, 2010). Albino teleosts are rare in nature and most of the studies on light-induced photodegeneration in fish have focused on albino mutant zebrafish.…”

Neural inflammation and the microglial response in diabetic retinopathy

“…As the neuronal pruning diminishes, the monocytes undergo a morphological shift, developing processes of increased length and branching. In the mature retina, the microglia appear primarily in two stratified arrays within the inner plexiform layer and one stratified array within the outer plexiform layer [12,13]. These fully ramified microglia are evenly distributed with extended process arbors that effectively span the space between adjacent microglia with minimal overlap [14].…”