Biomarkers of Neurodegeneration and Precision Therapy in Retinal Disease

Abstract

Vision-threatening retinal diseases affect millions of people worldwide, representing an important public health issue (high social cost) for both technologically advanced and new-industrialized countries. Overall RD group comprises the retinitis pigmentosa, the age-related macular degeneration (AMD), the diabetic retinopathy (DR), and idiopathic epiretinal membrane formation. Endocrine, metabolic, and even lifestyles risk factors have been reported for these age-linked conditions that represent a “public priority” also in this COVID-19 emergency. Chronic inflammation and neurodegeneration characterize the disease evolution, with a consistent vitreoretinal interface impairment. As the vitreous chamber is significantly involved, the latest diagnostic technologies of imaging (retina) and biomarker detection (vitreous) have provided a huge input at both medical and surgical levels. Complement activation and immune cell recruitment/infiltration as well as detrimental intra/extracellular deposits occur in association with a reactive gliosis. The cell/tissue aging route shows a specific signal path and biomolecular profile characterized by the increased expression of several glial-derived mediators, including angiogenic/angiostatic, neurogenic, and stress-related factors (oxidative stress metabolites, inflammation, and even amyloid formation). The possibility to access vitreous chamber by collecting vitreous reflux during intravitreal injection or obtaining vitreous biopsy during a vitrectomy represents a step forward for an individualized therapy. As drug response and protein signature appear unique in each single patient, therapies should be individualized. This review addresses the current knowledge about biomarkers and pharmacological targets in these vitreoretinal diseases. As vitreous fluids might reflect the early stages of retinal sufferance and/or late stages of neurodegeneration, the possibility to modulate intravitreal levels of growth factors, in combination to anti-VEGF therapy, would open to a personalized therapy of retinal diseases.

Effects of Vitamin D3 and Meso-Zeaxanthin on Human Retinal Pigmented Epithelial Cells in Three Integrated in vitro Paradigms of Age-Related Macular Degeneration

“…Therefore, in search of an improved formulation of supplements, we hereby explored for the first time, in an integrated in vitro model of AMD, the effects of 1,25(OH) 2 D 3 (vitamin D 3 ) and meso-zeaxanthin combination on several endpoints related to inflammation, oxidative stress, and cellular damage: amyloid β, H 2 O 2 , and inflammatory insults, that is, LPS and TNFα. The rationale of these integrated in vitro models of AMD is behind its multifactorial pathogenic etiology (Bucolo et al, 2006;Di Filippo et al, 2014;Fisichella et al, 2016;Platania et al, 2017Platania et al, , 2019Romano et al, 2017; Micera et al, 2021), involving amyloid-β and oxidative stress, has already been mentioned. As regards as, the LPS challenge is widely used as an experimental model of AMD, involving the activation of Toll-like receptor 4 (TLR-4) and the downstream activation of NFκB (Sung et al, 2019;Hikage et al, 2021), and then triggering the expression of inflammatory cytokines.…”

Searching for the Antioxidant, Anti-Inflammatory, and Neuroprotective Potential of Natural Food and Nutritional Supplements for Ocular Health in the Mediterranean Population

“…Neurodegeneration refers to the progressive damage and loss of both the structure and function of nerve cells and the vascular system, occurring in specific sites of the central and peripheral nervous system and the neurosensory organs [15]. Retinal and optic nerve neurodegenerative diseases, the majority of them incurable, are increasing worldwide, representing a serious health problem and a big financial burden for the countries [6,12,[15][16][17][24][25][26][27], among them, the multifactorial sight-threatening retinal and optic nerve diseases: AMD, RD, glaucoma, retinitis pigmentosa, macular dystrophies, uveoretinitis, pathologic myopia, retinal vascular occlusion, as well as the optic neuropathies [6,12,[15][16][17][24][25][26][27][28][29][30][31][32].…”

Metabolomics in Retinal Diseases: An Update

“…As one of the most common forms of rod-cone dystrophy, RP is characterized by initial rod degeneration, followed by cone degeneration, resulting in night blindness as well as subsequent tunnel vision and photophobia, and culminating in complete blindness [137]. RP can be grouped into non-syndromic RP caused by mutant proteins implicated in some functional retinal processes, and syndromic RP with systemic manifestations resulting from relevant gene mutations in cells/tissues [138,139]. For instance, a recently identified peripherin rare haplotype variant can cause impairments of photoreceptor outer segment renewal and phototransduction [140], which is closely linked with retinitis pigmentosa punctata albescens (RPA), a non-syndromic retinal degeneration.…”