Introduction

1. Introduction Conclusion References Methods Methods 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 Results Results • 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. 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. Neuropathy 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. • 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). NGF- treated left eye at baseline. GRADE 4 NGF- treated left eye at day 14 GRADE 0.5 Representative corneal fluorescein images at baseline and following 14 days of NGF treatment. 1) Kaji Y. Prevention of diabetic keratopathy. British Journal of Ophthalmology 2005;89:254-255. 2) Flugel A, Matsumuro K, Neumann H, Klinkert WEF, Birnbacher R, Lassman H, Otten U, Wekerle H. Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration. European Journal of Immunology 2001;31:11-22. 3) http://jaxmice.jax.org/strain/001976.html.   4) Suwan-apichon O, Rizen M, Rangsin R, Herretes S, Reyes JMG, Lekhanont K, Chuck RS. Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. Investigative Ophthalmology and Visual Science 2006;47:133-139. 5) Kaiserman I, Kaiserman N, Nakar S, Vinker S. Dry eye in diabetic patients. American Journal of Ophthalmology 2005;139:498-503.   6) Nepp J, Abela C, Polzer I, Derbolav A, Wedrich A. Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca. Cornea 2000;19:487-491.  7) Joo MJ, Yuhan KR, Hyon JY, Lai H, Hose S, Sinha D, O’Brien TP. The effect of nerve growth factor on corneal sensitivity after laser in-situ keratomileusis. Archives of Ophthalmology 2004;122:1338-1341.  8) Jain S. Dry eye in diabetes. Diabetes Care 1998;21:1375-1376.  9) Fan H, Longacre A, Meng F, Patel V, Hsiao K, Koh JS, Levine JS. Cytokine dysregulation induced by apoptotic cells is a shared characteristic of macrophages from non-obese diabetic and systemic lupus prone mice. Journal of Immunology 2004;172:4834-4843. 10) Barile GR, Pachydaki SI, Tari SR, Lee SE, Donmoyer CM, Ma W, Rong LL, Buciarelli LG, Wendt T, Horig H, Hudson BE, Qu W, Weinberg AD, Yan SF, Schmidt AM. The RAGE axis in early diabetic retinopathy. Investigative Ophthalmology and Visual Science 2005;46:2916-2924.  11) Lieth E, Gardner TW, Barber AJ, Antonetti DA. Retinal neurodegeneration: an early pathology in diabetes. Clinical and Experimental Ophthalmology 2000;28:3-8.  12) Xiong C, Chen D, Liu J, Liu B, Li N, Zhou Y, Liang X, Ma P, Ye C, Ge J, Wang Z. A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride. Investigative Ophthalmology and Visual Science 2008;49: 1850-1856. 13) Shaw SG, Boden JP, Biecker E, Reichen J, Rothen B. Endothelin antagonism prevents diabetic retinopathy in NOD mice. A potential role of the angiogenic factor adrenomodulin. Experimental Biology and Medicine 2006;231:1101-1105.  • 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. 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.