Therapeutic targeting of the complement system in ocular disease

Rathi, Sonika; Hasan, Rafiq; Ueffing, Marius; Clark, Simon J.

doi:10.1016/j.drudis.2023.103757

Cited by 6 publications

(3 citation statements)

References 120 publications

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“…Fine control of intraocular complement activity is critical for avoiding unnecessary inflammation that would degrade the visual axis. Complement dysregulation has been implicated in the pathogenesis of many ocular diseases, which has been extensively described in multiple reviews ( 10 , 29 – 31 ). We highlight several diseases listed in Table 1 and then focus on a comprehensive discussion of complement activity in AMD, given the recent translational developments and approval of complement-based therapies.…”

Section: Complement Activity In Ocular Diseasementioning

confidence: 99%

“…It is a disease of the elderly; therefore, the global burden of AMD is projected to rise as the aging population increases, with 300 million people projected to be diagnosed with AMD by 2040 ( 33 ). Complement activity has been a major focus in the investigation into AMD pathogenesis, leading to better understanding of the role of complement in the aging retina and the development of novel therapeutics ( 14 , 29 , 34 , 35 ).…”

Section: Complement Activity In Ocular Diseasementioning

confidence: 99%

“…With the abundance of data pointing toward complement dysregulation as a driver in AMD pathogenesis, current investigations into AMD treatment have focused on targeting complement activity. While we limit our discussion here to therapeutics that have advanced to clinical trials, new therapeutics at all stages of investigation are the focus of several recent reviews ( 29 , 35 , 104 , 105 ). Interestingly, complement targets in AMD were the subject of clinical trials over a decade ago.…”

Section: Complement Targets In Atrophic Amdmentioning

confidence: 99%

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

Wilke,

Apte

2024

Journal of Clinical Investigation

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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.

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Section: Complement Activity In Ocular Diseasementioning

confidence: 99%