The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration

Pinazo-Durán, María Dolores; Muñoz‐Negrete, Francisco J.; Sanz-González, Silvia M.; Benítez-del-Castillo, Javier; Giménez-Gómez, R.; Valero-Velló, Mar; Zanón‐Moreno, Vicente; García-Medina, J.J.

doi:10.1016/bs.pbr.2020.07.004

Cited by 14 publications

(8 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypotensive treatments to reduce IOP are also being investigated, but they do not always prevent the irreversible course of the glaucoma neurodegeneration. 5 – 7 …”

mentioning

confidence: 99%

Sodium Hyaluronate-Induced Ocular Hypertension in Rats Damages the Direction-Selective Circuit and Inner/Outer Retinal Plexiform Layers

Noailles

Kutsyr

Mayordomo-Febrer

et al. 2022

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

Purpose To assess the changes in retinal morphology in a rat model of chronic glaucoma induced by ocular hypertension. Methods Intraocular pressure (IOP) was surgically increased through weekly injections of sodium hyaluronate (HYA) in the anterior eye chamber of the left eye of male Wistar rats, whereas the right eyes were sham operated (salt solution). During the 10-week experimental period, IOP was measured weekly with a rebound tonometer. Retinal cryosections were prepared for histological/immunohistochemical analysis and morphometry. Results IOP was higher in HYA-treated eyes than in sham-operated eyes along the 10-week period, which was significant from the fourth to the nineth week. Ocular hypertension in HYA-treated eyes was associated with morphologic and morphometric changes in bipolar cells, ON-OFF direction-selective ganglion cells, ON/OFF starburst amacrine cells, and inner plexiform layer sublamina. Conclusions Serial HYA treatment in the rat anterior eye chamber results in mild-to-moderate elevated and sustained IOP and ganglion cell death, which mimics most human open-angle glaucoma hallmarks. The reduced number of direction-selective ganglion cells and starburst amacrine cells accompanied by a deteriorated ON/OFF plexus in this glaucoma model could lend insight to the abnormalities in motion perception observed in patients with glaucoma.

show abstract

“…Hypotensive treatments to reduce IOP are also being investigated, but they do not always prevent the irreversible course of the glaucoma neurodegeneration. 5 – 7 …”

mentioning

confidence: 99%

Sodium Hyaluronate-Induced Ocular Hypertension in Rats Damages the Direction-Selective Circuit and Inner/Outer Retinal Plexiform Layers

Noailles

Kutsyr

Mayordomo-Febrer

et al. 2022

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, we compared neuroinflammation and its role in RGC loss between elevated IOP and systemic hypotension, which are the two main mechanisms of glaucoma found in glaucoma patients. For glaucoma with elevated IOP, previous reports have suggested that oxidative stress could induce neuroinflammation and subsequent apoptotic RGC death [ 39 ]. The associated cell death pathways were accompanied by NF-κB activation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II related glial cell activation and necroptosis of retinal ganglion cells after systemic hypotension in glaucoma

et al. 2022

View full text Add to dashboard Cite

The purpose of this study was to design an animal model mimicking glaucoma with hemodynamic instability and to identify involvement of angiotensin II (AngII) and associated changes of the retina. Systemic hypotension was induced in Sprague–Dawley rats by oral hydrochlorothiazide administration. Rats were sacrificed at 4, 8, and 12-week time points. AngII and receptor levels were examined in the serum and retina. To examine the relationship between glia activation and associated RGC death, biochemical analysis of GFAP, Iba-1, and necroptosis associated factors such as TNFα, receptor-interacting protein (RIP) 1, 3, and inactive caspase 8 were explored. To investigate the difference in RGC death mechanism, JNK inhibitor or RIP3 inhibitor were given intraperitoneally to rats with ocular hypertension and systemic hypotension both to identify the pathway mainly involved. AngII and receptors were increased in the serum and retina of systemic hypotensive rat. At 4, 8, and 12 weeks after hypotension induction, glial activation was increased as indicated by GFAP and Iba-1 staining. TNFα, RIP3 were elevated. and downregulation of inactive caspase 8 was apparent in the retina of hypotensive rat. Electron microscopy revealed that necroptosis of RGC was gradually increased after systemic hypotension. Following intraperitoneal JNK inhibitor or RIP3 inhibitor administration, RGC loss was attenuated in systemic hypotensive rats but not in ocular hypertensive rats. In conclusion, AngII is involved in glial activation and associated RGC necroptosis following systemic hypotension. This pathway represents a novel and distinct cell death mechanism when compared to that involved in elevated intraocular pressure.

show abstract

“…Additionally, antioxidants can act as classical defenses, and as sensors of intracellular oxidants and regulators of the redox signaling [10,11]. It has widely been reported that ROS and RNS are involved in signal transduction pathways of proliferation and differentiation, inflammation and immune response, angiogenesis, metabolic dysfunction, and neurodegeneration processes, in the eyes [7][8][9][12][13][14][15][16][17].…”

Section: State Of the Artmentioning

confidence: 99%

“…The microglia of the central nervous system protect the organs and tissues under normal conditions, by responding swiftly to the injury signals. However, these activities are reverted in chronic neurodegenerative diseases, where the activated microglia are shifted on a pro-inflammatory phenotype that, in turn, release pro-inflammatory cytokines and different neurotoxic substances such as ROS and RNS, proteolytic enzymes, specific neurotransmitters, and others [12,[15][16][17]22,24].…”

Section: State Of the Artmentioning

confidence: 99%

“…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].…”

Section: State Of the Artmentioning

confidence: 99%

See 1 more Smart Citation

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

Valero-Velló

Peris-Martínez

García-Medina

et al. 2021

Foods

Self Cite

View full text Add to dashboard Cite

Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue “Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables,” is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.

show abstract

The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration

Cited by 14 publications

References 118 publications

Sodium Hyaluronate-Induced Ocular Hypertension in Rats Damages the Direction-Selective Circuit and Inner/Outer Retinal Plexiform Layers

Sodium Hyaluronate-Induced Ocular Hypertension in Rats Damages the Direction-Selective Circuit and Inner/Outer Retinal Plexiform Layers

Angiotensin II related glial cell activation and necroptosis of retinal ganglion cells after systemic hypotension in glaucoma

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

Contact Info

Product

Resources

About