Vascular dysfunction in retinitis pigmentosa

Lang, Matt; Harris, Alon; Ciulla, Thomas A.; Siesky, Brent; Patel, Pooja; Belamkar, Aditya; Mathew, Sunu; Vercellin, Alice Chandra Verticchio

doi:10.1111/aos.14138

Cited by 26 publications

(27 citation statements)

References 41 publications

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“…The first group of diseases is characterized by vasopermeability excess eventually leading to neovascularization, then resulting in retinal cell death (for Ref., see [6]). RP is characterized by photoreceptor degeneration associated with remodeling of blood vessels that undergo a process of progressive atrophy opposite to neovascularization typical of ischemia-associated degenerative pathologies [7]. Both groups of diseases share common chronic inflammatory processes that are mediated by Müller and microglial cells that, in response to retinal injuries, become activated, and the production and release of inflammatory cytokines increases [8,9].…”

Section: Degenerative Diseases Of the Retinamentioning

confidence: 99%

The uPAR System as a Potential Therapeutic Target in the Diseased Eye

Cammalleri

Monte

Pavone

et al. 2019

Cells

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Dysregulation of vascular networks is characteristic of eye diseases associated with retinal cell degeneration and visual loss. Visual impairment is also the consequence of photoreceptor degeneration in inherited eye diseases with a major inflammatory component, but without angiogenic profile. Among the pathways with high impact on vascular/degenerative diseases of the eye, a central role is played by a system formed by the ligand urokinase-type plasminogen activator (uPA) and its receptor uPAR. The uPAR system, although extensively investigated in tumors, still remains a key issue in vascular diseases of the eye and even less studied in inherited retinal pathologies such as retinitis pigmantosa (RP). Its spectrum of action has been extended far beyond a classical pro-angiogenic function and has emerged as a central actor in inflammation. Preclinical studies in more prevalent eye diseases characterized by neovascular formation, as in retinopathy of prematurity, wet macular degeneration and rubeosis iridis or vasopermeability excess as in diabetic retinopathy, suggest a critical role of increased uPAR signaling indicating the potentiality of its modulation to counteract neovessel formation and microvascular dysfunction. The additional observation that the uPAR system plays a major role in RP by limiting the inflammatory cascade triggered by rod degeneration rises further questions about its role in the diseased eye.

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Section: Degenerative Diseases Of the Retinamentioning

confidence: 99%

The uPAR System as a Potential Therapeutic Target in the Diseased Eye

Cammalleri

Monte

Pavone

et al. 2019

Cells

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“…The most common pathogenesis of RP is mainly associated with different gene mutations [5]; other causes include oxidative stress, Vitamin A deficiency, and immune and inflammatory response [6–8]. Furthermore, reduced retinal blood flow has been reported in RP patients, suggesting altered retinal blood flow to be an underlying factor in the pathology of RP [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Optical Coherence Tomography Angiography Assessed Retinal and Choroidal Microvasculature Features in Patients with Retinitis Pigmentosa: A Meta-Analysis

Ling

Gao

et al. 2019

BioMed Research International

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Background The aim of this study was to assess the retinal and choroidal microvasculature features using optical coherence tomography angiography (OCTA) in patients with retinitis pigmentosa (RP). Methods This study was a meta-analysis of relevant published studies that were included after a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases. Mean difference (MD) with a 95% confidence interval was used to assess continuous variable outcomes. Heterogeneity was evaluated using the chi-squared test based on the values of P and I2. Results Seven studies were included in this meta-analysis. The vessel density values measured in the superficial and deep foveal zones of RP patients using OCTA were significantly lower than the recorded values in the control groups (MD = −3.58, P=0.04; MD = −4.93, P=0.02, respectively). The superficial and deep parafoveal vessel density values measured with OCTA were also significantly lower in RP patients than in control groups (MD = −9.09, P < 0.00001; MD = −10.74, P < 0.00001, respectively); for choriocapillaris vessel density, there was no statistically significant difference between RP patients and controls (MD = −1.33, P=0.09). The deep foveal avascular zone (FAZ) was significantly larger in RP patients than in controls (MD = 0.15, P=0.01), whereas there was no significant difference in the superficial foveal avascular zones in the two groups (MD = 0.08, P=0.11). Conclusions We showed that retinal and choroidal vessels were attenuated in RP patients. Additionally, we revealed that the FAZ was larger in RP patients, especially the deep FAZ. OCTA may become a useful modality in the diagnosis and monitoring of patients with RP.

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“…Retinal degeneration diseases are conditions wherein progressive neuronal loss is responsible for symptom onset, with the most common form being retinitis pigmentosa (RP) as it is the leading cause of inherited retinal degeneration-associated blindness, affecting approximately 1.5 million people worldwide [1].With the advent of next generation sequencing and recent advances in gene therapy, the identified mutant genes responsible for RP show signs of a growth spurt [2]. Gene therapy for RP is limited by the heterogeneous genetic basis for this disease, highlighting the importance of developing therapies that function independently of mutation status [3].…”

Section: Introductionmentioning

confidence: 99%

Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

Sun

Liu

et al. 2020

Preprint

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Background : To explore the impact of Ferulic acid (FA) on microglia-mediated neuroinflammation as well as associated retinal degeneration by using a rd10 mouse model as a means. Methods : Rd10 mice received different concentrations of FA treatment every day from postnatal day (P)4 to P24. At P25, mice visual function were detected by electroretinogram, then retinae were collected for further investigation. Retinal microglia activation state and relevant cytokines were evaluated by qPCR, Western blot and immunofluorescent staining. The retinal structure was assessed by HE Staining. Results :50mg/kg FA supplement exhibited optimal protection against retinal degeneration, with treated mice exhibiting more photoreceptor nuclei as well as significant wave amplitude amplification in electroretinograms. FA suppressed microglia activation both in vivo and in vitro , inhibited pro-inflammatory factors Tnfα, IL1β, Ccl2 expression in rd10 retinae. Furthermore, FA suppressed the activation of STAT1 and subsequently IRF8 expression, potentially highlighting a role for these pathways in FA-mediated immunomodulatory activity. Conclusions : Attenuating neuroinflammation by FA may be beneficial to retard retinal degeneration.

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Vascular dysfunction in retinitis pigmentosa

Cited by 26 publications

References 41 publications

The uPAR System as a Potential Therapeutic Target in the Diseased Eye

The uPAR System as a Potential Therapeutic Target in the Diseased Eye

Optical Coherence Tomography Angiography Assessed Retinal and Choroidal Microvasculature Features in Patients with Retinitis Pigmentosa: A Meta-Analysis

Ferulic acid attenuates microglia-mediated neuroinflammation in retinal degeneration

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