MINI REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1623755
This article is part of the Research TopicRetinal Degenerative Diseases: Processes and Potential TreatmentsView all 6 articles
Sialylation as a checkpoint for inflammatory and complement-related retinal diseases
Provisionally accepted- 1Institute of Reconstructive Neurobiology, Medical Faculty & University Hospital Bonn, University of Bonn, Bonn, Germany
- 2Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany
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Sialylation, a modification involving the addition of sialic acid sugars to the terminus of glycoproteins and glycolipids in mammalian cells, serves as a crucial checkpoint inhibitor of the complement and immune systems, particularly within the central nervous system (CNS), including the retina. Complement factor H (FH), complement factor properdin (FP), and sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors of retinal mononuclear phagocytes are key players in the regulation of complement and innate immune systems in the retina, by recognizing sialic acid residues. Intact retinal sialylation prevents any long-lasting and excessive complement or immune activation in the retina. However, sialylated glycolipids are reduced in the CNS during aging and may contribute to chronic inflammatory processes in the retina. Particularly, genetically induced hyposialylation in mice leads to age-related and complement factor C3-mediated retinal inflammation and bipolar cell loss. Notably, most of the gene transcript pathways enriched in the mouse retina following genetically induced hyposialylation are also involved in age-related macular degeneration (AMD). Interestingly, intravitreal application of polysialic acid (polySia) controlled innate immune responses in the mouse retina by blocking mononuclear phagocyte reactivity, inhibiting complement activation, and protecting against vascular damage in two different humanized SIGLEC-11 animal models. Accordingly, a polySia polymer conjugate has entered clinical phase II/III testing in patients with geographic atrophy secondary to AMD. Thus, hyposialylation or dysfunctional sialylation should be considered as an age-related contributor for inflammatory retinal diseases such as AMD. Consequently, sialic acid-based biologics might be promising novel therapies for complement-related retinal diseases.
Keywords: Retina, sialylation, sialic acid, polysialic acid, complement, Microglia, Inflammation, Age related macular degeneration (AMD)
Received: 06 May 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Min, Cuevas-Rios, Langmann and Neumann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Harald Neumann, Institute of Reconstructive Neurobiology, Medical Faculty & University Hospital Bonn, University of Bonn, Bonn, Germany
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