Aim: Preliminary serum exosomal proteomics of patients with dry age-related macular degeneration (AMD) and mild cognitive impairment (MCI) were analyzed using proteomics technology.

Methods: Peripheral serum samples were collected from patients with AMD, MCI, comorbid conditions, and the control group. Exosomes were isolated from these samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) associated with the two diseases were identified based on fold change and p-value. DEPs were analyzed by Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to validate the DEPs of interest.

Inclusion Criteria:

• All dry AMD patients were diagnosed based on the Clinical Classification of Age-Related Macular Degeneration issued by the American Academy of Ophthalmology.

All patients with MCI meet the Petersen criteria, including memory impairment, no abnormal cognitive function, dementia, or some cognitive impairment in daily life. A Mini-Mental State Examination (MMSE) score ≥24 points and a Montreal Cognitive Assessment (MoCA) score between 18 and 25 points were required.

Exclusion Criteria:

• The systemic physical exclusion criteria were as follows:(a) Metabolic syndromes such as diabetes or obesity;(b) Uncontrolled hypertension or hypotension;(c) Serious cardiac disease;(d) Neurological diseases, including Parkinson's disease, multiple sclerosis, or peripheral neuropathy;(e) Psychiatric diseases such as hallucinations or depressive disorders;(f) a history of brain injury, stroke, or substance abuse.

The ocular exclusion criteria were as follows: (a) intraocular pressure(IOP) > 21 mmHg; (b) axial length(AL) > 25 mm or <22 mm; (c) anterior segment disease affecting fundus examination; (d) retinal pathologic changes associated with high myopia or serious refractive errors (>5D of spherical equivalent refraction or >3D of astigmatism); (e) concomitant ocular diseases, such as glaucoma or retinal detachment; (f) other genetic ocular diseases; and (g) other fundus diseases, including macular hiatus, macular edema, retinal vascular occlusion, or central serous chorioretinopathy.

patients who attended the Department of Ophthalmology or Department of Neurology of Shanghai Tenth People's Hospital affiliated with Tongji University School of Medicine