Para-inflammation in the aging retina

Xu, Heping; Chen, Mei; Forrester, John V.

doi:10.1016/j.preteyeres.2009.06.001

Cited by 558 publications

(550 citation statements)

References 244 publications

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“…Additionally, age‐related inflammatory changes are believed to contribute to the pathogenesis of DR (Xu et al. 2009). This could make patients with an older age of onset of T1DM more vulnerable to development of complications.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus

Schreur

Asten

et al. 2018

Acta Ophthalmologica

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PurposeTo investigate risk factors for the development and progression of diabetic retinopathy (DR) and long‐term visual outcomes in Dutch patients with type 1 diabetes mellitus (T1DM).MethodsCumulative incidences were calculated for DR, vision‐threatening DR (VTDR), defined as (pre)proliferative DR and diabetic macular oedema, and best‐corrected visual acuity (BCVA) <0.5 and <0.3 at the most recent eye examination. The following factors were assessed: duration of diabetes, age of onset of T1DM, gender, mean HbA1c, HbA1c variability (defined as coefficient of variation of five separate HbA1c measurements), mean arterial blood pressure, body mass index, albuminuria and lipid profile. We used multivariable Cox regression models to identify factors associated with DR development and progression to VTDR.ResultsWe found 25‐year cumulative incidences of 63% for DR, 21% for VTDR, 2% for BCVA <0.5, and 1% for BCVA <0.3. Mean HbA1c (HR 1.023, p < 0.001), HbA1c variability (HR 1.054, p < 0.001), age of onset of T1DM (HR 1.024, p < 0.001), HDL cholesterol (HR 0.502, p = 0.002) and total cholesterol (HR 1.210, p = 0.029) showed an independent association with faster development of any form of DR. The mean HbA1c (HR 1.023, p < 0.001) and the presence of albuminuria (HR 2.940, p = 0.028) were associated with faster progression to VTDR.ConclusionThese data show relatively low cumulative incidences of DR, VTDR and visual impairment. Higher mean HbA1c, HbA1c variability, age of onset of T1DM and total cholesterol were independently associated with the risk of DR development, and a protective association was found for HDL cholesterol in subjects with T1DM. Mean HbA1c and presence of albuminuria were associated with progression of DR.

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Section: Discussionmentioning

confidence: 99%

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus

Schreur

Asten

et al. 2018

Acta Ophthalmologica

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“…At present, vision loss results mostly from macular edema, which is associated with breakdown of retinal barriers and with photoreceptor dysfunction and/or loss. 2,3 It has also been clearly established that immune imbalance and local inflammation 4,5 participate in pathogenic events during the course of diabetes, 5 contributing to the loss of photoreceptors and visual impairment.…”

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confidence: 99%

“…6 The RPE is a selective exchange platform between the systemic circulation and the retina, and the subretinal space between RPE and the neuroretina is considered as an immune-privileged site. 5 Microglial cells, the main resident sentinel immune cells, are located in the inner part of the retina, around vessels in the healthy retina. [7][8][9][10][11][12] These cells become activated and migrate in the subretinal space in several retinopathies such as diabetic retinopathy, 13,14 age-related macular degeneration, 15 and aging.…”

mentioning

confidence: 99%

“…[7][8][9][10][11][12] These cells become activated and migrate in the subretinal space in several retinopathies such as diabetic retinopathy, 13,14 age-related macular degeneration, 15 and aging. 5,16,17 The activation of microglia induced by hyperglycemia has been associated with the early development of DR. Indeed, it has been reported that, under diabetic conditions, retinal microglia activation occurs as early as electroretinographic modifications.…”

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confidence: 99%

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Microglia/Macrophages Migrate through Retinal Epithelium Barrier by a Transcellular Route in Diabetic Retinopathy

Omri

Behar‐Cohen

Kozak

et al. 2011

The American Journal of Pathology

173

124

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Diabetic retinopathy is associated with ocular inflammation, leading to retinal barrier breakdown, macular edema, and visual cell loss. We investigated the molecular mechanisms involved in microglia/macrophages trafficking in the retina and the role of protein kinase C (PKC ) in this process. Goto Kakizaki (GK) rats, a model for spontaneous type 2 diabetes were studied until 12 months of hyperglycemia. Up to 5 months, sparse microglia/macrophages were detected in the subretinal space, together with numerous pores in retinal pigment epithelial (

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“…Although the majority of disease burden from vision loss derives from the advanced forms of AMD, it is known that drusen accumulation starts decades earlier and may promote a chronic state of parainflammation in the outer retina (Hageman et al, 2001;Lin et al, 2013;Xu et al, 2009). Therefore, effective early AMD intervention requires the understanding of these inflammatory events and the identification of valid cellular targets.…”

Section: Discussionmentioning

confidence: 99%

Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells

Liu

Wang

et al. 2014

Experimental Eye Research

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Chronic inflammation is a key pathogenic process in age-related macular degeneration (AMD). Amyloid-beta (Aβ) is a constituent of AMD drusen and promotes the activation of NLRP3 inflammasome which facilitates the production of cytokines. We investigated the role of transcription factor NF-κB in the activation of inflammasome in the RPE and the effect of vinpocetine, a dietary supplement with inhibitory effect on NF-κB. ARPE19/NF-κB-luciferase reporter cells treated with Aβ demonstrated enhanced NF-κB activation that was significantly suppressed by vinpocetine. Intraperitoneal injection of vinpocetine (15 mg/kg) inhibited NF-κB nuclear translocation and reduced the expression and activation of NLRP3, caspase-1, IL-1β, IL-18, and TNF-α in the RPE of adult rats that received intraocular Aβ, as measured by retinal immunohistochemistry and Western blot. Cytokine level in the vitreous was assayed using multiplex suspension arrays and revealed significantly lower concentration of MIP-3α, IL-6, IL-1α, IL-1β, IL-18, and TNF-α in vinpocetine treated animals. These results suggest that the NF-κB pathway is activated by Aβ in the RPE and signals the priming of NLRP3 inflammasome and the expression of pro-inflammatory cytokines including the inflammasome substrates IL-1β and IL-18. NF-κB inhibition may be an effective approach to stem the chronic inflammatory milieu that underlies the development of AMD. Vinpocetine is a potentially useful anti-inflammatory agent that is well-tolerated in long term use.

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Para-inflammation in the aging retina

Cited by 558 publications

References 244 publications

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus

Microglia/Macrophages Migrate through Retinal Epithelium Barrier by a Transcellular Route in Diabetic Retinopathy

Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells

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