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Aging-US: Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration

09-08-2021

Aging-US published a Special Collection on Eye Disease which included "Activation of C-reactive protein proinflammatory phenotype in the blood retinal barrier in vitro: implications for age-related macular degeneration" which reported that the retinal pigment epithelium (RPE) is considered one of the main targets of age-related macular degeneration (AMD), the leading cause of irreversible vision loss among the ageing population worldwide. Increased levels of circulating pentameric C-reactive protein (pCRP) are associated with higher risk of AMD. Monomeric form of pCRP has been detected in drusen, the hallmark deposits associated with AMD, and we have found that mCRP induces oBRB disruption

Dr. Blanca Molins from The IDIBAPS, Hospital Clínic de Barcelona said, "Age-related macular degeneration (AMD) is the primary cause of irreversible vision loss among the ageing population worldwide."

AMD presents RPE cell abnormalities, disruption of the outer blood-retinal-barrier (oBRB), and degeneration of photoreceptors. Altered immune responses are thought to contribute to the dry AMD phenotype. Loss of parainflammation control contributes to AMD by invoking a chronic, heightened immune response that causes tissue destruction. mCRP has been identified in ocular drusen and other subepithelial deposits, as well as in the choroid, and contributes to oBRB disruption in vitro.

The "non-risk" Factor H (FH) variant can effectively bind to mCRP to dampen its proinflammatory activity. MCRP levels are elevated in individuals with the high-risk CFH genotype [29, 30] - this is because there is no CRP transcription in retinal tissue.

The "non-risk" Factor H (FH) variant can effectively bind to mCRP to dampen its proinflammatory activity. MCRP levels are elevated in individuals with the high-risk CFH genotype

The Molins Research Team concluded in their https://www.aging-us.com/article/103655/">Aging-US Research Output, "our findings further support mCRP direct contribution to progression of AMD, at least at the RPE level. The topological experiments elicit that mCRP is proinflammatory when present on the apical side of the RPE. However, mCRP is likely to only reach the apical side of the RPE in compromised RPE health and where barrier functions are compromised. Thus, a plausible scenario would infer that, in the presence of an already aged/damaged RPE, mCRP reaches the apical side of the RPE to amplify the proinflammatory microenvironment and enhance barrier disruption. With respect to previous findings, this pathologic mechanism will be more prevalent in patients carrying the FH risk polymorphism for AMD, where mCRP proinflammatory effects remain unrestrained."

Figure 6. mCRP induces barrier disruption in primary porcine RPE cells in a polarized manner. Primary porcine RPE cells were treated with CRP isoforms for 48h either from the apical side or the basolateral chamber and TEER (A) and paracellular permeability as determined by FITC-dextran diffusion rate (B) was determined. (C) Cells were then fixed and immunostained with anti ZO-1 (red) and DAPI (blue). Images shown are representative of four independent experiments. Arrows show disruption of ZO-1. Scale bar = 20 μm. (D) Quantification of ZO-1 at the TJs expressed as relative (intercellular/cytoplasmic) ZO-1 distribution. Values are expressed as mean ± SD and statistical analysis was performed by one-way ANOVA and Dunnett´s posthoc analysis (N=6). * P<0.05, ** P<0.01, *** P<0.0001 vs. control.

Full Text - https://www.aging-us.com/article/103655/text

Correspondence to: Blanca Molins email: bmolins@clinic.cat

Keywords: age-related macular degeneration, retinal pigment epithelium, inflammation, C-reactive protein

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