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Updated: Mar 27, 2026
Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023
The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal Neovascularization and Subretinal Fibrosis
Ruoshuang Zhang1, Zheli Liu1, Han Zhang1
1Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
Abstract:
Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium-choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-β2 in the retinal pigment epithelium-choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-β2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis.
Insights
Cyclooxygenase-2 (COX-2) inhibition with NS-398 reduced choroidal neovascularization (CNV) and subretinal fibrosis in models of age-related macular degeneration (AMD). This occurred by decreasing macrophage infiltration, VEGF, and TGF-β2, offering a potential therapeutic strategy.
Area of Science:
- Ophthalmology
- Molecular Biology
- Immunology
Background:
- Choroidal neovascularization (CNV) and subretinal fibrosis are key features of neovascular age-related macular degeneration (AMD), leading to vision loss.
- The exact molecular mechanisms driving CNV and fibrosis in AMD remain unclear.
- Cyclooxygenase-2 (COX-2) is implicated in angiogenesis and fibrosis, but its specific role in AMD pathogenesis is poorly understood.
Purpose of the Study:
- To investigate the role of COX-2 in the development of CNV and subretinal fibrosis.
- To evaluate the efficacy of COX-2 inhibition as a therapeutic strategy for AMD-related complications.
Main Methods:
- Experimental CNV and subretinal scarring models were established.
- Mice were treated with NS-398, a selective COX-2 inhibitor.
- Macrophage infiltration, VEGF, and TGF-β2 levels were assessed in retinal pigment epithelium-choroid complexes.
- Mouse RPE cells were cultured to examine VEGF and TGF-β2 secretion.
Main Results:
- Administration of NS-398 significantly attenuated experimental CNV lesions.
- NS-398-mediated CNV suppression was linked to reduced macrophage infiltration and decreased VEGF levels.
- NS-398 also reduced subretinal fibrosis by down-regulating TGF-β2.
- In cultured RPE cells, NS-398 decreased the secretion of both VEGF and TGF-β2.
Conclusions:
- COX-2 signaling plays a significant role in the pathogenesis of CNV and subretinal fibrosis in AMD.
- Inhibition of COX-2 with NS-398 demonstrates a potential therapeutic approach for treating CNV and subretinal fibrosis.
- Targeting COX-2 may offer a novel strategy to combat vision loss associated with neovascular AMD.
