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Complement regulation in the eye: implications for age-related macular degeneration
Georgia A. Wilke, Rajendra S. Apte
Georgia A. Wilke, Rajendra S. Apte
Published May 1, 2024
Citation Information: J Clin Invest. 2024;134(9):e178296. https://doi.org/10.1172/JCI178296.
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Review

Complement regulation in the eye: implications for age-related macular degeneration

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Abstract

Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). In the last two decades, complement activity has been the focus of intense investigation in AMD pathogenesis, leading to the development of novel therapeutics for the treatment of atrophic AMD. This Review outlines recent advances and challenges, highlighting therapeutic approaches that have advanced to clinical trials, as well as providing a general overview of the complement system in the posterior segment of the eye and selected ocular diseases.

Authors

Georgia A. Wilke, Rajendra S. Apte

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Figure 2

The retina consists of specialized cell types organized into layers.

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The retina consists of specialized cell types organized into layers.
(A)...
(A) The outer retina consists of photoreceptors, while the inner retina contains bipolar, amacrine, horizontal, Müller, and retinal ganglion cells. Bipolar cells synapse with photoreceptors and transmit their signal to ganglion cells. Horizontal and amacrine cells regulate photoreceptor and bipolar cells, respectively. Müller cells are the glial/support cells of the retina. The retina is supported by the retinal pigment epithelium (RPE). The basal lamina of the RPE forms part of Bruch’s membrane (BM), a multilayered ECM. (B) Pathological changes in early AMD occur in BM and the RPE. Basal laminar deposits appear between the RPE and the RPE basal lamina; basal linear deposits form in the inner collagenous zone of BM. Drusen are deposits beneath the RPE basal lamina; they contain cellular debris, including lipids, proteins, and complement components, such as C3, C5, and MAC (denoted by the asterisk) (74). Subretinal drusenoid deposits form anterior to the RPE and are associated with an accelerated neurodegenerative phenotype in AMD.

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