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      Neuroprotective factors of the retina and their role in promoting survival of retinal ganglion cells: a review

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          Abstract

          Retinal ganglion cells (RGC) play a crucial role in the visual pathway. As their axons form the optic nerve, apoptosis of these cells causes neurodegenerative vision loss. RGC death could be triggered by increased intraocular pressure, advanced glycation end products, or mitochondrial dysfunction. In this review, we summarize the role of some neuroprotective factors in RGC injury: ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glial cell line-derived neurotrophic factor (GDNF), and Norrin. Each, in their own unique way, prevents RGC damage caused by glaucoma, ocular hypertension, ischemic neuropathy, and even oxygen-induced retinopathy. These factors are produced mainly by neurons, leukocytes, glial cells, and epithelial cells. Neuroprotective factors act via various signaling pathways, including JAK/STAT, MAPK, TrkA, and TrkB, which promotes RGC survival. Many attempts have been made to develop therapeutic strategies using these factors. There are ongoing clinical trials with CNTF and NGF, but they have not yet been accepted for clinical use.

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          Most cited references126

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          The retinal pigment epithelium in visual function.

          Located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, the retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. Increasing knowledge of the multiple functions performed by the RPE improved the understanding of many diseases leading to blindness. This review summarizes the current knowledge of RPE functions and describes how failure of these functions causes loss of visual function. Mutations in genes that are expressed in the RPE can lead to photoreceptor degeneration. On the other hand, mutations in genes expressed in photoreceptors can lead to degenerations of the RPE. Thus both tissues can be regarded as a functional unit where both interacting partners depend on each other.
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            The types of retinal ganglion cells: current status and implications for neuronal classification.

            In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that most RGCs are not merely light detectors, but rather feature detectors, which send a diverse set of parallel, highly processed images of the world on to higher centers. Here, we review progress in classification of RGCs by physiological, morphological, and molecular criteria, making a particular effort to distinguish those cell types that are definitive from those for which information is partial. We focus on the mouse, in which molecular and genetic methods are most advanced. We argue that there are around 30 RGC types and that we can now account for well over half of all RGCs. We also use RGCs to examine the general problem of neuronal classification, arguing that insights and methods from the retina can guide the classification enterprise in other brain regions.
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              SOCS3 deletion promotes optic nerve regeneration in vivo.

              Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Ophthalmic Research
                Ophthalmic Res
                S. Karger AG
                0030-3747
                1423-0259
                January 15 2021
                Article
                10.1159/000514441
                2f21b99e-dedb-4e6c-83fc-8f0d78d5fa29
                © 2021

                https://creativecommons.org/licenses/by-nc-nd/4.0/

                https://creativecommons.org/licenses/by-nc-nd/4.0/

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