TY - JOUR
T1 - Complement regulation in the eye
T2 - implications for age-related macular degeneration
AU - Wilke, Georgia A.
AU - Apte, Rajendra S.
N1 - Publisher Copyright:
© 2024, Wilke et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85192034528&partnerID=8YFLogxK
U2 - 10.1172/JCI178296
DO - 10.1172/JCI178296
M3 - Review article
C2 - 38690727
AN - SCOPUS:85192034528
SN - 0021-9738
VL - 134
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 9
M1 - e178296
ER -