May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Remodeling of the Neurovascular Unit in the Aging Inner Retina
Author Affiliations & Notes
  • A. Wang
    Ophthalmology, Northwestern University, Chicago, Illinois
  • M. Yuan
    Ophthalmology, Northwestern University, Chicago, Illinois
  • W. Luo
    Ophthalmology, Northwestern University, Chicago, Illinois
  • T. Lukas
    Ophthalmology, Northwestern University, Chicago, Illinois
  • A. H. Neufeld
    Ophthalmology, Northwestern University, Chicago, Illinois
  • Footnotes
    Commercial Relationships A. Wang, None; M. Yuan, None; W. Luo, None; T. Lukas, None; A.H. Neufeld, None.
  • Footnotes
    Support NIH12017
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4463. doi:
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    • Get Citation

      A. Wang, M. Yuan, W. Luo, T. Lukas, A. H. Neufeld; Remodeling of the Neurovascular Unit in the Aging Inner Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4463.

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

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Abstract

Purpose:: Age as a risk factor for neuronal damage suggests intrinsic changes in neurons and/or in their supporting cells. With age, there is an incremental decrease in retinal blood flow and an increase in the susceptibility to damage of the inner retina following retinal ischemia/reperfusion and optic nerve crush. Maintaining the homeostasis of the inner retinal environment is a function of the retinal neurovascular unit (rNV), a functional unit composed of neurons of the ganglion cell layer (GCL), astrocytes, microglia, Muller cell endfeet and microvasculature cells. In this study, we address the cellular and molecular changes in the rNV of the aging inner retina.

Methods:: The phenotypic changes with age in the structure of the astrocytes, microglia, Muller cell endfeet and capillaries were studied by Immunohistochemistry, Immunofluorescence and confocal microscopy using flat mounts and/or paraffin sections. The ultrastructure of the rNV with age was studied by electron microscopy. The changes on the molecular level were studied by western blot and immunofluorescence.

Results:: In 22 month, all layers of the retina decrease in thickness. In the inner retina, there are remodeling of the rNVs associated with thinning of the nerve fiber layer (NFL) and decreased numbers of neurons in the GCL with age. In old rNVs, the microvasculature is tortuous and there is increased capillary density. With age, there are decreased numbers of astrocytes in the parenchymal tissue and an associated loss of connexin 43 (Cx 43). The remaining perivascular astrocytes are large with thick short processes. In aged rNVs, markers for astrocyte/capillary interaction, such as Kir 4.1 and aquaporin 4, increase. There are also marked morphological changes in microglia and the Muller cell endfeet in aged retinas.

Conclusions:: With age, there is remodeling of the rNV suggesting an altered relationship between astrocytes and capillaries. Astrocytes with fine terminal processes that are coupled through gap junctions (Cx 43) are lost in the aged NFL. Thus, intercellular pathways for diffusion of ions and small molecules may be compromised. The increased size of perivascular astrocytes and the increases of Kir 4.1 (K+ channels) and aquaporin 4 (water channels) suggest increased activity of the astrocytes in the aged NFL to maintain K+ and water homeostasis. These functions are crucial for supporting neuronal activity. Changes in homeostatic mechanisms within the rNV may contribute to the age-related increased susceptibility of neurons in the GCL.

Keywords: aging • astrocyte • blood supply 
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