Age-related macular degeneration (AMD) is one of the leading causes of vision impairment and blindness in the elderly worldwide, with its prevalence increasing significantly with age. The pathogenesis of AMD is multifactorial, involving genetic predisposition, environmental risk factors, chronic inflammation, and mitochondrial dysfunction. In recent years, mitophagy has emerged as a critical mechanism for maintaining mitochondrial quality control, energy homeostasis, and cellular integrity in retinal pigment epithelium (RPE) and photoreceptor cells. Dysregulated mitophagy leads to the accumulation of damaged mitochondria, excessive reactive oxygen species, and metabolic imbalance, thereby triggering RPE dysfunction, inflammatory amplification, and choroidal neovascularization, which drive AMD progression. Both classical pathways (e.g., PINK1/Parkin) and non-classical pathways (e.g., BNIP3, FUNDC1) have been implicated in AMD pathophysiology. Molecules such as Parkin and p62, as well as multimodal imaging features, hold promise as early biomarkers for disease monitoring. Preclinical studies have shown that small-molecule activators (e.g., Urolithin A, Spermidine) and mitochondria-targeted antioxidants (e.g., MitoQ, SkQ1) can restore mitophagy and alleviate RPE damage. However, current evidence remains limited, as large-scale, long-term clinical trials are lacking. Challenges in drug delivery efficiency, safety, patient stratification, and clinical monitoring tools still hinder translation into practice. Future research should focus on biomarker-driven precision interventions, multicenter randomized controlled trials, and individualized therapeutic strategies. Overall, mitophagy research is transitioning from mechanistic exploration to clinical translation, with promising potential to enable early diagnosis, disease stratification, and precision management of AMD.
ObjectiveTo observe the electroretinogram (ERG) photopic negative response (PhNR) of idiopathic macular hole (IMH) in stage 2 by vitrectomy with or without internal limiting membrane peeling (ILMP).MethodsTwenty-three stage 2 IMH patients (23 eyes) were enrolled in this prospective study. All patients received the best corrected visual acuity (BCVA), optical coherence tomography and flash-ERG examinations. The patients were randomly divided into group A (11 eyes, vitrectomy) and B (12 eyes, vitrectomy with ILMP). There was no significant difference in BCVA (t=0.96, P=0.350), diameter of macular hole (MH) (t=3.21, P=0.580) and the PhNR amplitude (t=0.98, P=0.353) in group A and B. All patients underwent 25G vitrectomy, ILMP was carried out in group B. The follow-up time was 3 to 6 months, with the mean follow-up time of 4.3 months. BCVA, MH closure rate and PhNR amplitude in group A and B were analyzed before and after surgery.ResultsThree months after surgery, 10 eyes (90.9%) gained MH closure but 1 eye (9.1%) failed in group A. In group B, 12 eyes (100.0%) gained MH closure. There was no significant difference in MH closure rate between the two groups (P=0.462). The mean BCVA of group A and B was 0.69±0.24 and 0.65±0.22, there was no significant difference between the two groups (t=0.49, P=0.722). The amplitude of PhNR in group A was (36.6±7.4) μV, which was lower than the pre-surgery PhNR, but the difference was not significant (t=0.73, P=0.472). The amplitude of PhNR in group B was (27.1±12.4) μV, which was lower than that the pre-surgery PhNR, and the difference was significant (t =3.56, P =0.002). The difference of PhNR amplitude in group A and B was statistically significant (t=2.17, P=0.042).ConclusionCompared with non-ILMP, vitrectomy combined with ILMP will significantly reduce the PhNR amplitude of IMH in stage 2.