C-Reactive Protein as a Therapeutic Target in Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD), a retinal degenerative disease, is the leading cause of central vision loss among the elderly population in developed countries and an increasing global burden. The major risk is aging, compounded by other environmental factors and association with genetic variants for risk of progression. Although the etiology of AMD is not yet clearly understood, several pathogenic pathways have been proposed, including dysfunction of the retinal pigment epithelium, inflammation, and oxidative stress. The identification of AMD susceptibility genes encoding complement factors and the presence of complement and other inflammatory mediators in drusen, the hallmark deposits of AMD, support the concept that local inflammation and immune-mediated processes play a key role in AMD pathogenesis that may be accelerated through systemic immune activation. In this regard, increased levels of circulating C-reactive protein (CRP) have been associated with higher risk of AMD. Besides being a risk marker for AMD, CRP may also play a role in the progression of the disease as it has been identified in drusen, and we have recently found that its monomeric form (mCRP) induces blood retinal barrier disruption in vitro. In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile

“…The prognostic impact of CRP shows that the acute phase reaction is important in renal cell carcinoma [ 39 , 58 , 59 , 60 ]. CRP is not only a marker but also a mediator with distinct biological functions [ 61 , 62 , 63 ]. However, the systemic acute phase reaction is a very complex response, and the aim of our present study was, therefore, to investigate the systemic levels of acute phase cytokines in renal cancer patients with a focus on the acute phase cytokine profiles, rather than those of single cytokines.…”

Novel Association of High C-Reactive Protein Levels and A69S at Risk Alleles in Wet Age-Related Macular Degeneration Women

“…In line with this, monomeric-CRP has shown to induce an inflammatory phenotype ( 50 ) and blood–retinal barrier disruption in RPE cells ( 51 ). Given the similarities of risk factors between CVD and AMD, this approach could be considered as a local adjuvant therapy in future new strategies for patients at greater risk, such as women with high CRP levels and at-risk A69S genotype ( 52 ). This could contribute to a better quality of life and reduce personal burden for AMD patients.…”

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

“…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 [28].…”

“…Moreover, we also showed that the “non-risk” Factor H (FH) variant can effectively bind to mCRP to dampen mCRP pro-inflammatory activity [ 27 ]. Notably, FH from AMD patients carrying the risk polymorphism for AMD shows an impaired binding to mCRP and, therefore, its proinflammatory effects remain unrestrained [ 28 ]. In line with these findings, data demonstrates that mCRP is the more abundant form of CRP in human RPE-choroid [ 29 ], and that mCRP levels are elevated in individuals with the high-risk CFH genotype [ 29 , 30 ].…”