Inflammation in Age-Related Macular Degeneration – Implications for Therapy

Chen, Mei; Xu, Heping

doi:10.5772/25658

Cited by 3 publications

(1 citation statement)

References 99 publications

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“…We found that in the Mmp‐9 loss‐of‐function mutants, the survival of regenerated cone photoreceptors is compromised. It is well established that chronic inflammation is a risk factor for photoreceptor dystrophies in humans, such as retinitis pigmentosa and age‐related macular degeneration (AMD; Kauppinen, Paterno, Blasiak, Salminen, & Kaarniranta, ; Chen & Xu, ; Whitcup, Nussenblatt, Lightman, & Hollander, ; Yoshida et al, ). A subset of patients with AMD exhibit single nucleotide polymorphism (SNP) variants in the MMP‐9 gene, and elevated inflammation is associated with AMD pathogenesis (Fritsche et al, ; Kauppinen et al, ; Parks et al, ).…”

Section: Discussionmentioning

confidence: 99%

Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2020

Glia

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Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the zebrafish retina and determine the cellular expression and function of the inflammatory protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Following photoreceptor ablation, anti-inflammatory treatment suppresses the number of injury-induced progenitors and regenerated photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over production of injury-induced progenitors and regenerated photoreceptors, but over time the absence of Mmp-9 compromises the survival of the regenerated cones. At all time-points studied, the levels of tnf-α are significantly elevated in mutant retinas.Anti-inflammatory treatment in mutants rescues the defects in cone survival. These data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function during neuronal regeneration and the requirement of Mmp-9 for the survival of regenerated cones.

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Section: Discussionmentioning

confidence: 99%

Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2020

Glia

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Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Silva

Nagashima

et al. 2019

Preprint

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51Brain injury activates complex inflammatory signals in dying neurons, surviving neurons, and 52 glia. Here, we establish that inflammation regulates the regeneration of photoreceptors in the 53 zebrafish retina and determine the cellular expression and function of the inflammatory 54 protease, matrix metalloproteinase 9 (Mmp-9), during this regenerative neurogenesis. Animals 55 of either sex were used in this study. Following photoreceptor ablation, anti-inflammatory 56 treatment suppresses the number of injury-induced progenitors and regenerated 57 photoreceptors. Upon photoreceptor injury, mmp-9 is induced in Müller glia, the intrinsic retinal 58 stem cell, and Müller glia-derived photoreceptor progenitors. Deleting mmp-9 results in over 59 production of injury-induced progenitors and regenerated photoreceptors, but over time the 60 absence of Mmp-9 compromises the maturation and survival of the regenerated cones. Anti-61 inflammatory treatment in mutants rescues the defects in cone maturation and survival. These 62 data provide a link between injury-induced inflammation in the vertebrate CNS, Mmp-9 function 63 during photoreceptor regeneration and the requirement of Mmp-9 for the survival of regenerated 64 cones. 65 66 67 68 69 70 71 72 73 74 75 3 Significance Statement 76 77 The innate immune system is activated by neuronal death, and recent studies demonstrate that 78 in zebrafish neuroinflammation is required for neuronal regeneration. The roles of inflammatory 79 cytokines are being investigated, however, the function of the inflammatory protease, matrix 80 metalloprotease Mmp-9, in neuronal regeneration is unknown. We show herein that in adult 81 zebrafish retinal inflammation governs the proliferative phase of the stem cell-based 82 regeneration of rod and cone photoreceptors and determine the specific roles for Mmp-9 in 83 photoreceptor regeneration. This study provides the first mechanistic insights into the potential 84 role of Mmp-9 in retinal regeneration and serves to link neuroinflammation, stem cell-based 85 regeneration of photoreceptors and human photoreceptor disease. 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 2013; Zhao et al., 2014). Following a photolytic lesion, dying photoreceptors secrete Tnf-a, to 129 which Müller glia respond by partial dedifferentiation, synthesis of Tnf-a and entry into the cell 130 cycle (Nelson et al., 2013). Mechanical lesions induce the expression of leptin and Il-6 family 131 cytokines in Müller glia and Müller glia-derived progenitors and is required for injury-induced 132 proliferation (Zhao et al., 2014).133 Matrix metalloproteinase 9 (Mmp-9) is a secreted protease that plays a prominent role in 134 tissue development and homeostasis by acting on extracellular molecules, including adhesion 135

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Etiopathogenesis of non-exudative age-related macular degeneration (literature review)

Бикбов

Khalimov

2022

Acta biomedica scientifica

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The article presents an overview of modern publications on epidemiology, risk factors, and the main links of the etiology and pathogenesis of age-related macular degeneration (AMD). The nonexudative or “dry” form of age-related macular degeneration is a multifactorial progressive pathological process caused by hereditary predisposition, general and local disorders of lipid metabolism, negative changes in the blood supply to the eye, age-related destruction of the Bruch’s membrane and retinal pigment epithelium, the appearance of signs of local and systemic inflammation, the development of oxidative stress with the impact of toxic lipoperoxidation products on the structures of the posterior segment of the eye. Recent studies have discovered new ways of retinal pigment epithelial cell death in response to oxidative stress in AMD, in particular necroptosis, which, in addition to classical apoptosis, is considered the main mechanism of this process. It is noted that the development of AMD may be associated with an age-related decrease in the level of estrogen in women. The analysis of the data on the etiopathogenesis of age-related macular degeneration presented in the modern literature indicates the need for further research and generalization of local and general pathological processes developing in the dynamics of retinal visual function disorders by specialists of various scientific disciplines.

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Inflammation in Age-Related Macular Degeneration – Implications for Therapy

Cited by 3 publications

References 99 publications

Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

Inflammation and matrix metalloproteinase 9 (Mmp‐9) regulate photoreceptor regeneration in adult zebrafish

Inflammation and matrix metalloproteinase 9 (Mmp-9) regulate photoreceptor regeneration in adult zebrafish

Etiopathogenesis of non-exudative age-related macular degeneration (literature review)

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