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(Investigative Ophthalmology and Visual Science. 2004;45:4174-4182.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0455
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Neuroprotective Effect of Hepatocyte Growth Factor against Photoreceptor Degeneration in Rats

Shigeki Machida,1 Michiko Tanaka,1 Takehisa Ishii,2 Kouji Ohtaka,1 Tomomi Takahashi,1 and Yutaka Tazawa1

1From the Department of Ophthalmology, Iwate Medical University School of Medicine, Iwate, Japan; and the 2Discovery Technology Laboratory, R&D Division Mitsubishi Pharma Corp., Kanagawa, Japan.

PURPOSE. To determine whether hepatocyte growth factor (HGF) has a neuroprotective effect against photoreceptor degeneration in rats.

METHODS. Eight-week-old Sprague-Dawley (SD) and 24-day-old Royal College of Surgeons (RCS) rats received an intravitreal injection of HGF in the right eyes. The left eyes were injected with vehicle and served as the control. Two days after the injections, the SD rats were exposed to fluorescent light of 3000 lux for 72 hours. Scotopic and photopic electroretinograms (ERGs) were recorded 2 weeks after the light damage and at 70 days of age in RCS rats. After the ERG recordings, the animals were killed for histologic analysis. Some RCS rats were killed at 2 weeks after HGF-treatment for TdT-dUTP terminal nick-end labeling (TUNEL) studies.

RESULTS. In both light-damaged and RCS rats, the thresholds for the scotopic and photopic b-wave were significantly lower in the HGF-treated eyes than in the control eyes (P < 0.02). The maximum b-wave amplitudes (Vbmax) of the scotopic and photopic ERGs were significantly larger in the HGF-treated eyes (P < 0.0005) with a significantly greater number of photoreceptor nuclei than in the control eyes in both animal models (P < 0.005). The vehicle-injected eyes of RCS rats had significantly larger numbers of TUNEL-positive photoreceptor nuclei than the HGF-treated eyes (P = 0.005).

CONCLUSIONS. Intravitreal HGF led to the morphologic and physiological preservation of photoreceptors in rats with photoreceptor degeneration induced by phototoxicity or a gene mutation. The antiapoptotic effect may be the mechanism for the neuroprotective action of HGF.




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