Topical nerve growth factor ameliorates experimental type 1 diabetic keratopathy.Shannon Hextrum1, Bruce Gaynes, O.D., PharmD1,2 , Ping Bu, MD1,2 , Andrew Logeman1

1Edward Hines, Jr. VA Hospital, Hines, Illinois 2Loyola University Stritch School of Medicine, Department of Ophthalmology, Maywood, IL

Introduction

References

Methods Results ConclusionNeuropathy is a primary cause of many of the complications related to diabetes mellitus, including recalcitrant neurotrophic keratopathy due to abnormal corneal nerve conductance as well as dysfunction in retinal electrical signaling.1

Nerve growth factor (NGF) is a signaling neurotrophin that plays an important role in promoting nerve development, regulating inflammatory responses, and maintaining appropriate nerve function.2 Based on the known supportive role of NGF in maintaining physiologic nerve activity, it is hypothesized that NGF would be of benefit in ameliorating keratitis associated with diabetes mellitus.

Treatment animals showed marked improvement of epithelial damage by day 14, with all mice showing staining of less than or equal to grade one. While PBS-treated mice showed improvement from baseline by day 14, the results were modest compared to NGF-treated mice. In conclusion, NGF appears to improve keratitis associated with experimental models of type 1 diabetes mellitus.

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•Ten nonobese diabetic mice from the Jackson Laboratory (NOD/LtJ) were used for this study.3 Blood glucose was markedly elevated at baseline in all mice. The study protocol was as follows: •Treatment Group: 5μL NGF was applied to both eyes of each mouse, 3X daily, for 14 days. •Control Group: 5 μL PBS was applied to both eyes of each control mouse, 3X daily, for 14 days. •Both Groups received 5 μL of benzalkonium chloride on the left eye only, in order to exacerbate the effects of diabetic dry eye. This was applied 2X daily from day 3-14.

•Corneal Staining: was performed with topical application of sodium fluorescein followed by corneal imaging with a conventional digital camera on a dissecting microscope at baseline, day 7, and day 14.

Methods

NGF- treated left eye at baseline.GRADE 4 NGF- treated left eye at day 14

GRADE 0.5

•Grading System: (grades 0-5) of epithelial damage were assigned to all photographs based on standardized fluorescein staining criteria developed by Olan Suwan-apichon et al.4 (5=maximal staining, 0=no staining).

Results

Acknowledgments:

We would like to acknowledge the support of the Illinois Society for the Prevention of Blindness, the Richard A. Perritt Charitable Foundation and the Loyola University STAR research program for the conduct of this work. In addition, Phillip Williams and Christine Staunton provided significant help in handling and caring for the mice.

Representative corneal fluorescein images at baseline and following 14 days of NGF treatment.