Melanopsin Ganglion Cells Are the Most Resistant Retinal Ganglion Cell Type to Axonal Injury in the Rat Retina

Müller, Luis Pérez de Sevilla; Sargoy, Allison; Rodriguez, Allen; Brecha, Nicholas C.

doi:10.1371/journal.pone.0093274

Cited by 84 publications

(72 citation statements)

References 57 publications

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“…Interestingly, the melanopsin-mediated PLR (inferred ipRGC function) was not selectively spared in our diabetic patients, contrary to previous reports of selective ipRGC resistance to injury4142 and disease144344. In fact, ipRGC dysfunction appears to be a relatively early indicator of abnormality, as some diabetics who had mild NPDR had melanopsin-mediated PLRs that were outside of the normal range.…”

Section: Discussioncontrasting

confidence: 99%

Pupillary responses in non-proliferative diabetic retinopathy

Park

Chen

Blair

et al. 2017

Sci Rep

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The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

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Section: Discussioncontrasting

confidence: 99%

Pupillary responses in non-proliferative diabetic retinopathy

Park

Chen

Blair

et al. 2017

Sci Rep

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“…There is confounding evidence in the literature about the susceptibility of the large RGCs to cell death. Large RGCs were relatively spared in a model of axonal injury (Perez de Sevilla Muller et al, 2014). In contrast, in a glaucoma model induced by chronic elevation of intraocular pressure (IOP), the large RGCs showed greater susceptibility and tended to be more severely damaged compared to smaller RGCs (Quigley et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush

Wang

Chan

Qin

et al. 2015

Experimental Eye Research

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Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.

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“…The PACAP expression in this subset of ganglion cells is partly controlled by dopamine, while it is not affected by photoreceptor degeneration [ 25 , 26 ]. Melanopsin-containing retinal ganglion cells are known to be more resistant in various types of degeneration, such as axonal injury [ 27 ], and it has been proven by numerous studies that these melanopsin-containing cells almost all co-store PACAP, which might contribute to the highly resistant nature of these cells [ 28 -30 ]. PACAP-and melanopsin-containing retinal ganglion cells play an important role in several light-activated non-image-forming functions of the retina and the complimentary signaling due to PACAP neurotransmission has been shown to be important in addition to the glutamatergic signaling [ 31 , 32 ].…”

Section: Distribution Of Pacap In the Retinamentioning

confidence: 99%

Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, infl ammation, and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N -methyl-D -aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-infl ammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases.

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Melanopsin Ganglion Cells Are the Most Resistant Retinal Ganglion Cell Type to Axonal Injury in the Rat Retina

Cited by 84 publications

References 57 publications

Pupillary responses in non-proliferative diabetic retinopathy

Pupillary responses in non-proliferative diabetic retinopathy

Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush

Protective Effects of PACAP in the Retina

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