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Nerve Growth Factor Prevents Both Neuroretinal Programmed Cell Death and Capillary Pathology in Experimental Diabetes

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Abstract

Background

Chronic diabetes causes structural changes in the retinal capillaries of nearly all patients with a disease duration of more than 15 years. Acellular occluded vessels cause hypoxia, which stimulates sight-threatening abnormal angiogenesis in 50% of all type I diabetic patients. The mechanism by which diabetes produces acellular retinal capillaries is unknown.

Materials and Methods

In this study, evidence of programmed cell death (PCD) was sought in the retinas of early diabetic rats, and the effect of nerve growth factor (NGF) on PCD and capillary morphology was evaluated.

Results

Diabetes induced PCD primarily in retinal ganglion cells (RGC) and Muller cells. This was associated with a transdifferentiation of Muller cells into an injury-associated glial fibrillary acidic protein (GFAP)-expressing phenotype, and an up-regulation of the low-affinity NGF receptor p75NGFR on both RGC and Muller cells. NGF treatment of diabetic rats prevented both early PCD in RGC and Muller cells, and the development of pericyte loss and acellular occluded capillaries.

Conclusions

These data provide new insight into the mechanism of diabetic retinal vascular damage, and suggest that NGF or other neurotrophic factors may have potential as therapeutic agents for the prevention of human diabetic retinopathy.

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Acknowledgments

This work was supported by National Institutes of Health Grant DK 33861-07, the Juvenile Diabetes Foundation, and Grant Hal755/1-1 from the Deutsche Forschungsgemeinschaft. We would like to thank Dr. John A. Kessler, Albert Einstein College of Medicine, for making NGF-treated animal tissue available to us.

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Authors and Affiliations

  1. III. Medizinische Klinik und Poliklinik, Zentrum fur Innere Medizin, Justus-Liebig-Universitat, Giessen, Germany

    Hans-Peter Hammes

  2. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA

    Howard J. Federoff

  3. Diabetes Research Center, F531, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Michael Brownlee

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  1. Hans-Peter Hammes
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  2. Howard J. Federoff
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  3. Michael Brownlee
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Hammes, HP., Federoff, H.J. & Brownlee, M. Nerve Growth Factor Prevents Both Neuroretinal Programmed Cell Death and Capillary Pathology in Experimental Diabetes. Mol Med 1, 527–534 (1995). https://doi.org/10.1007/BF03401589

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