July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Adipose tissue derived stem cell concentrated conditioned medium alters the expression pattern of glutamate regulatory proteins and aquaporin-4 in retina after mild traumatic brain injury
Author Affiliations & Notes
  • Kumar Abhiram Jha
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Jordy Gentry
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Anton Reiner
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
    Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health science center, Memphis, Tennessee, United States
  • Rajashekhar Gangaraju
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
    Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health science center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Kumar Abhiram Jha, None; Jordy Gentry, None; Anton Reiner, None; Rajashekhar Gangaraju, Cell Care Therapeutics (F)
  • Footnotes
    Support  DOD Grant W81XWH-16-1-0778
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3329. doi:
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      Kumar Abhiram Jha, Jordy Gentry, Anton Reiner, Rajashekhar Gangaraju; Adipose tissue derived stem cell concentrated conditioned medium alters the expression pattern of glutamate regulatory proteins and aquaporin-4 in retina after mild traumatic brain injury. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3329.

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

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Abstract

Purpose : Stem cell therapies for neurodegenerative diseases show the promise of retinal regeneration. Previously we have shown that intravitreal injection of human adipose tissue derived stem cell concentrated conditioned medium (ASC-CCM) protected against the visual deficits of mild traumatic brain (mTBI) injury. Glutamate, a neurotransmitter and Aquaporin-4 (AQP-4), a water channel protein are fundamental to retinal homeostasis. In this study, we hypothesized that ASC-CCM can rescue retinal damage and thereby improve visual function through the glutamine synthetase (GS), L-glutamate aspartate transporter-1 (GLAST) and AQP-4 in Müller cells in mTBI.

Methods : About 12 weeks old C57Bl/6 mice were subjected to 50-psi air pulse on the left side of the head, resulting in an mTBI. Sham-blast mice served as control. After blast injury, 1 µl of human ASC-CCM was delivered intravitreally. After 4 weeks, eyes were enucleated and processed for immunofluorescence, western blot and qRT-PCR studies. Efficacy of ASC-CCM in normalizing rat retinal Muller cells activated by Glutamate was tested in vitro.

Results : Immunofluorescence analysis of equal area of retina demonstrated decreased expression of GS (56.10±6.56 vs 31.29±1.78; p<0.003) and increased expression of AQP-4 (8.68±1.53 vs 31.24±5.32; p<0.003) in Müller cell processes in the blast group as compared to sham. On the other hand, blast group animals that received ASC-CCM reversed GS (31.29±1.78 vs 47.68 ± 2.96; p<0.04) and AQP-4 (31.24±5.32 vs 12.77 ± 6.81; p<0.038) expression. While gene expression by Taqman PCR and protein expression by Western blot demonstrated decreased GS, GLAST and an increase in AQP-4 in blast group compared to sham group, blast group that received ASC-CCM restored them. In-vitro, rMC-1 Müller glia exposed to 100 ng/mL glutamate increased GFAP with 12 h (a marker of gliosis); while it is reduced by ASC-CCM pretreatment.

Conclusions : Taken together with our previous observation of improvement in visual response, our data suggests a neuroprotective role for ASC-CCM in the rescue of visual deficits of mTBI via alteration of GS, GLAST, and AQP-4. Identification of potential clinical endpoints and mechanism of action of ASC-CCM will likely help us translate these studies into clinic to preserve the vision in soldiers with blast injuries.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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