Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.

Journal: Neural regeneration research
Published Date: Oct 30, 2025

Abstract

Dysregulated proteome in the retina represents a promising avenue for discovering novel therapeutic targets and noninvasive diagnostic biomarkers for neurodegenerative diseases with ocular manifestations. Advanced mass spectrometry-based proteomics techniques have shown considerable potential in investigating the retinal proteome in diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, as well as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Recent proteomics innovations are overcoming challenges such as limited sample size and protein coverage that previously hindered comprehensive retinal proteome analysis. Notably, the incorporation of artificial intelligence-driven computational pipelines, including Graphics Processing Unit-accelerated deep learning architectures, has markedly enhanced the precision and effectiveness of retinal proteomics. These advances facilitate high-resolution identification of novel protein signatures within large-scale multi-omics datasets. Furthermore, the integration of advanced artificial intelligence with state-of-the-art big data infrastructures supports the early detection of biomarkers and therapeutic targets in neurodegenerative diseases with ocular involvement, offering unprecedented disease specificity and sensitivity. In addition to these computational strides, emerging complementary and alternative technologies continue to provide valuable tools for retinal analysis, expanding the potential for identifying biomarker and therapeutic targets in both ophthalmic and neurodegenerative disorders. This review summarizes recent advancements in retinal proteomics, with a particular focus on neurodegenerative and ocular diseases.

Authors

  • Shahab Mirshahvaladi
    Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Bhakta Prasad Gaire
    Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Sara Assar Kashani
    MND Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Aparajeeta Guha
    Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Yosef Koronyo
    Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Dieu-Trang Fuchs
    Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Yuyi You
    Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, Australia; Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. Electronic address: [email protected].
  • Keith L Black
    Department of Neurosurgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., AHSP, Los Angeles, CA 90048, United States; Department of Biomedical Sciences, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States.
  • Joao A Paulo
    Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Stuart L Graham
    Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
  • Vivek Gupta
    From the Department of Radiology, Mayo Clinic, Jacksonville, FL, USA (Z.L., X.Z., S.T., E.M.W., V.G., E.H.M.); Department of Radiology, Peking Union Medical College Hospital, Beijing, China (Z.L.); Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland (T.Y.); Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (T.Y.); LTS5, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland (T.Y.); Siemens Medical Solutions USA, Inc., Jacksonville, FL, USA (J.M.); MR Application Predevelopment, Siemens Healthineers AG, Forchheim, Germany (P.L.); Siemens Medical Solutions USA, Inc., Scottsdale, AZ, USA (H.M.); Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA (H.M.).
  • Mehdi Mirzaei
    Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
  • Maya Koronyo-Hamaoui
    Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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