The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

Abstract

Retinal neurodegeneration is predominantly reported as the apoptosis or impaired function of the photoreceptors. Retinal degeneration is a major causative factor of irreversible vision loss leading to blindness. In recent years, retinal degenerative diseases have been investigated and many genes and genetic defects have been elucidated by many of the causative factors. An enormous amount of research has been performed to determine the pathogenesis of retinal degenerative conditions and to formulate the treatment modalities that are the critical requirements in this current scenario. Encouraging results have been obtained using gene therapy. We provide a narrative review of the various studies performed to date on the role of inflammation in human retinal degenerative diseases such as age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. In addition, we have highlighted the pivotal role of various inflammatory mechanisms in the progress of retinal degeneration. This review also offers an assessment of various therapeutic approaches, including gene-therapies and stem-cell-based therapies, for degenerative retinal diseases.

CD3+CD4-CD8- Double-Negative Lymphocytes Are Increased In The Aqueous Humour Of Patients Affected By Retinitis Pigmentosa: Their Possible Role In Mediating Inflammation

“…Of note, red blood cells were virtually absent in all the samples evaluated, thus excluding blood contamination. Therefore, our data support the hypothesis of a role of in ammation in the pathogenesis of RP, in agreement with literature (23) Interestingly, the cell composition of AH was limited to MNCs; moreover, lymphocyte composition was different from that found in the blood sample of the same patients, with a signi cant reduction of NK cells, of CD4 + Th cells and with a signi cant increase of CD3 + CD4-CD8-T cells, mainly made up of TCRαβ lymphocytes.…”

“…Moreover, the corneal endothelium and retina do not express the Major histocompatibility complex (MHC) class I molecules and are a potential target of cytotoxic activity by NK cells; this could represent the starting point or the progression of an in ammatory condition. It has been shown that the aqueous humour contains a wide range of soluble factors inhibiting immune response, in particular NK-mediated cytotoxicity, the main being represented by TGF-b (23,24). We could speculate that the ocular micro-enviroment contributes to reducing the frequency of NK cells in order to maintain tissue protection and support the immunological privilege.…”

Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications

“…The various harmful stimuli are detected by retinal immune cells through engagement with pattern recognition receptors, including pathogen-associated molecular patterns and damage-associated molecular patterns, which respond by upregulating myriad inflammatory genes [ 25 ]. Four classes of pathogen recognition receptor families have been described to date: Toll-like receptors, C-type lectin receptors, retinoic acid-inducible gene (RIG)-I-like receptors, and NOD-like receptors [ 26 ].…”

“…Similar to other degenerative CNS diseases, the major contributors to IRD-related inflammation and cell death are TNF-𝛼 and interleukin (IL)-1. TNF-𝛼 is a key factor secreted in the retina by activated microglia and macrophages [ 25 ] and can trigger different cell-death mechanisms, including apoptosis, pyroptosis, necroptosis, and parthanatos [ 25 , 28 ].…”

Regenerative Strategies for Retinal Neurons: Novel Insights in Non-Mammalian Model Organisms

“…Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the retinal pigment epithelium (RPE), while mammalian RPE is limited in its regenerative capacity. RPE inflammatory events highly participate in neurodegenerative progress, and RPE dysfunction or disease can lead to blindness in humans [ 16 ]. Of interest, macrophage/microglia cells have been recently shown to be responsive to RPE damage in zebrafish, and their function is required for the timely progression of the RPE regenerative response [ 17 ].…”