June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Progenitor cells in the adult human retina
Author Affiliations & Notes
  • Lili Gerendas
    Department of Anatomy, Histology and Embryology, Semmelweis Egyetem, Budapest, Budapest, Hungary
    Department of Ophthalmology, Semmelweis Egyetem, Budapest, Budapest, Hungary
  • Barbara Asboth
    Department of Anatomy, Histology and Embryology, Semmelweis Egyetem, Budapest, Budapest, Hungary
    Department of Ophthalmology, Semmelweis Egyetem, Budapest, Budapest, Hungary
  • Daniel Magda
    Department of Anatomy, Histology and Embryology, Semmelweis Egyetem, Budapest, Budapest, Hungary
    BrainVisionCenter Knowledge and Competence Centre, Budapest, Budapest, Hungary
  • Ferenc Kilin
    Department of Anatomy, Histology and Embryology, Semmelweis Egyetem, Budapest, Budapest, Hungary
    BrainVisionCenter Knowledge and Competence Centre, Budapest, Budapest, Hungary
  • Zoltán Zsolt Nagy
    Department of Ophthalmology, Semmelweis Egyetem, Budapest, Budapest, Hungary
  • Arnold Szabo
    Department of Anatomy, Histology and Embryology, Semmelweis Egyetem, Budapest, Budapest, Hungary
    BrainVisionCenter Knowledge and Competence Centre, Budapest, Budapest, Hungary
  • Footnotes
    Commercial Relationships   Lili Gerendas None; Barbara Asboth None; Daniel Magda None; Ferenc Kilin None; Zoltán Zsolt Nagy None; Arnold Szabo None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5230. doi:
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    • Get Citation

      Lili Gerendas, Barbara Asboth, Daniel Magda, Ferenc Kilin, Zoltán Zsolt Nagy, Arnold Szabo; Progenitor cells in the adult human retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5230.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retinas of lower vertebrates have a certain degree of regenerative capacity. The main element of regeneration is the Muller cell which can generate new glia and neurons by entering the cell cycle and transforming into a multipotent progenitor stem cell. While it has been generally accepted that Muller cells in mammals have completely lost their progenitor nature and ability to divide, recent results from rodent models have challenged this view.
Currently, there is insufficient information on the regenerative capacity of Muller cells in the human retina.

Methods : Eyes of adult multi-organ organ donors without known ocular disease were removed within an hour of cardiac arrest and subjected to immunohistochemistry using mitotic, progenitor, and cell-type-specific markers after fixation. We designed the experiments so that the periphery, and central region of the retina can be compared.

Results : The Ki-67 proliferation marker detected a significant amount of dividing cells, and a subset of them expressed Pax6 protein, indicating their retinal origin. A small fraction of dividing cells colocalized the Muller cell-specific Sox9 protein. Notable colocalization was found with protein Iba-1, which marks microglial cells. The expression of Sox2, Pax6, and S100β proteins showed a significantly decreasing gradient from the periphery to the centre. Sox2 and Pax6 markers showed high level of colocalization in inner retinal cells. The anti-S100β antibody labelled a subgroup of Muller cells. Labelling with the Muller cell- specific Sox9 protein revealed co-expression of Sox2 and Pax6 proteins in 22.5% of peripheral Muller cells.

Conclusions : To our knowledge, we are the first to demonstrate that Muller cell division occurs in vivo in the original, intact, three-dimensional environment, without the addition of growth or other stimulatory factors. A subset of peripheral Muller cells exhibits characteristics of retinal progenitor cells, and at least a fraction of Muller cells retains the ability to divide in adulthood.
These findings raise the possibility that selective, vector-mediated transduction of Muller cells could be used to induce their division in a targeted and controlled manner. Based on the results of experiments in rodent models, it may be feasible in the future to replace lost retinal neurons by genetically reprogramming the generated cells.
A therapy based on this principle could be potentially applicable to several, degenerative retinal diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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