Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the industrialized world. According to relevant statistics, by 2040, the number of people suffering from AMD will reach more than 280 million (Fleckenstein et al., 2021; Wong et al., 2014). The main manifestations of early-intermediate stage AMD are retinal pigment abnormalities and subretinal drusenoid deposits. Most vision loss occurs in late AMD rather than early AMD, including atrophy of the outer retina, thinning, or even loss of the RPE layer, and the pathological progression of MNV (Spaide et al., 2020).

According to past reports, MNV is pathological neovascularization. In the initial stage of the development of MNV, the structure of Bruch's membrane has changed, which is the key condition for the development of the disease and represents the result of degenerative changes and inflammation of AMD (Chong, 2005). Chronic damage to the surrounding tissue is caused by newly formed and constantly leaking blood vessels, which consist of MNV, when they finally penetrate Bruch's membrane into the subretinal space. Simultaneously, an environment with a wealth of inflammatory mediators is created. The inflammatory environment culminates in excessive ECM accumulation, which is a primary distinction in fibrotic healing (Patel and Sheth, 2021; Wynn, 2007). Excessive fibrosis can form subretinal scars, lead to irreversible rupture of choroidal blood vessels, and even cause neuroretinal damage, which is the most serious reason for loss of vision in AMD patients (Tenbrock et al., 2022a). The pathogenesis of MNV and subretinal fibrosis is complicated and has not yet been completely clarified. In the early stage of AMD, Bruch's membrane can produce drusen/basal linear deposits. Then the retinal pigment epithelial cells migrate to the inner retina, which is the change of intermediate AMD. In late-stage AMD, geographic atrophy (GA) and macular neovascularization will occur. GA refers to the loss of photoreceptors, retinal pigment epithelium and choroidal capillaries and other atrophy manifestations. However, leakage or rupture of macular neovascularization after formation may lead to inter-retinal fluid accumulation and subretinal fluid accumulation. If MNV is not treated promptly, it can produce extensive fibrosis with severe vision loss (Age-related macular degeneration) (Fleckenstein et al., 2021). However, the current treatment for MNV mainly involves intravitreal injection of antivascular endothelial growth factor (VEGF), which not only requires repeated injections, but also, according to relevant studies, anti-VEGF therapy does not completely inhibit retinal destruction and fiber scarring (Li et al., 2023; Liu et al., 2023; Zandi et al., 2023). At present, there is little research on the pathogenesis of subretinal fibrosis, and there is still no clear method to inhibit MNV and prevent excessive fibrosis (Tenbrock et al., 2022b).

The ECM is the constituent component of the ocular microenvironment, which is fundamental and essential. The major components of the ECM include collagen, laminin, elastin, fibronectin, proteoglycan, and hyaluronic acid (Hubmacher and Apte, 2013; Yue, 2014). Fibronectin is a heterodimer cell adhesion molecule composed of two amino acid chains, each of which comprises structural units arranged adjacent to the other, which can be divided into three types. Fibronectin is an early component of the ECM and serves as an assembly template for other extracellular matrix proteins. Its expression is increased in angiogenesis and fibrosis (Leiss et al., 2008). FN, as a large molecular weight glycoprotein, recognizes and binds to cell surface integrin receptors through its arginine-aspartate-glycine (Arg-Gly-Asp, RGD) sequence, thereby affecting cell adhesion and migration (Kennelly et al., 2019). As a cell surface receptor, integrin is a heterodimer composed of 18 α subunits and 8 β subunits and is commonly used to mediate the ECM and reacts in proliferation, migration, and angiogenesis (Desgrosellier and Cheresh, 2010; Pankov et al., 2000). Therefore, integrin α5β1 is commonly used to bind to fibronectin and participate in angiogenesis in ailments such as tumors (Clark et al., 2005; X. Xu et al., 2023). However, it has not been confirmed whether FN and α5β1 bind in AMD and whether they play a role in MNV and fibrosis.

Therefore, in this study, a choroidal neovascularization model was set up to detect the expression changes of α5β1 in this disease by regulating FN expression and to verify the interaction of FN-α5β1 in this disease. The results showed that when the FN expression level was decreased, the degree of MNV pathological changes was distinctly reduced, the externalization of integrin α5β1 was also decreased, and the Wnt/β-catenin signaling pathway was inhibited. Therefore, FN is not only a key factor in fibrotic diseases but also takes effect in MNV; therefore, we believe that inhibiting FN expression may be a significant therapy target for MNV and subretinal fibrosis.