Melanin-Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age-Related Macular Degeneration.

Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis and subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing irreversible vision loss in the global elderly population. However, currently, no effective interventional treatment strategy exists in clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as a novel ferroptosis inhibitor for retinal degenerative diseases. ConA-MelNPs possessed chelating iron ion characteristics, alleviating severe mitochondrial damage caused by oxidative stress and protecting RPE cells from ferroptosis induced by sodium iodate (NaIO3). In a preclinical dAMD mouse model, a single intravitreal injection of ConA-MelNPs yielded significant responses in electroretinograms and visually-driven optomotor responses in visually impaired mice, resisting the challenge posed by secondary NaIO3-induced injuries, with the long-term sustainability of its therapeutic effect. Mechanistically, ConA-MelNPs achieve a therapeutic effect by interrupting the detrimental cascade involving "RPE cell ferroptosis, lethal oxidative stress, and microglial proinflammatory activation," affording the restoration of retinal homeostasis. The synthesized ConA-MelNPs demonstrated good biosafety, with no detected ophthalmic or systemic side effects. Collectively, ConA-MelNPs are proposed as a promising therapeutic option for atrophic retinal diseases such as dAMD.

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases.

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Impact of 24-Hour Intraocular Pressure on Optic Nerve Fiber Layer Thickness in Patients with Early Diabetic Retinopathy.

Background: The optic nerve fiber layer, composed of ganglion cell axons within the ganglion cell layer, undergoes thickness changes due to diabetic retinopathy. However, the relationship between intraocular pressure (IOP) and optic fiber layer thickness remains unclear. Objective: To investigate the correlation between 24-hour intraocular pressure and optic nerve fiber layer thickness in patients with early diabetic retinopathy. Methods: This retrospective study collected 353 patients with early diabetic retinopathy from January 2019 to December 2021. They were categorized into the retinopathy group (n = 153) and the control group (n = 200). 24-hour IOP and optic fiber layer thickness were assessed, and the correlation between them was analyzed. Results: The observation group exhibited significantly higher 24-hour IOP compared to the control group (16.64 ± 2.58 vs. 15.63 ± 2.52 mmHg, P < .001). Notably, the thickness of upper, lower, nasal, temporal, and average optic nerve fiber layers in the observation group decreased significantly (P < .001). Pearson linear correlation revealed significant negative associations between 24-hour IOP and upper, nasal, temporal, and mean optic nerve fiber layer thickness (R2 = -0.277, -0.399, -0.344, and -0.489, P < .05). The upper, lower, nasal, temporal, and mean optic fiber thickness demonstrated diagnostic value for non-early diabetic retinopathy in type 2 diabetes patients (P < .05), with mean optic fiber thickness displaying the highest diagnostic potential (area under the curve: 0.843, 95% Confidence Interval: 0.803-0.884, P < .001). Conclusions: Thinning of the optic nerve fiber layer in early diabetic retinopathy patients holds predictive value for the condition and exhibits a negative correlation with 24-hour intraocular pressure.