Abstract
Purpose:
Since its discovery nerve growth factor (NGF), a naturally occurring protein involved in the differentiation, growth and maintenance of neurons, has been considered a potential treatment for neurodegenerative disorders. Recent evidence suggests NGF may also be beneficial in ocular neurodegenerative diseases such as retinitis pigmentosa (RP) and glaucoma. A major limitation in the development of NGF for the treatment of ophthalmic diseases is the adequate production of a formulation capable of penetrating the globe or crossing the blood retinal/brain barrier. Herein, we report the effect of recombinant human NGF (rhNGF) administered intravitreally and topically on the progression of photoreceptor degeneration in a well-characterized model of RP.
Methods:
Royal College of Surgeons (RCS) rats were allocated 1 of 5 treatment groups (no treatment, rhNGF eye drops (200µg/ml) 3 times daily for 20 days, or one 5 µl intravitreal injection of either saline, murine NGF or rhNGF) with all treatments initiated at day 20, the onset of the retinal degeneration. At day 40 treated eyes were collected and evaluated using histopathology, immunohistochemistry, confocal microscopy, western blot and immunoenzymatic analysis.
Results:
Compared to controls, eyes treated with NGF (murine and rhNGF) showed a lower expression of apoptotic markers, reduced numbers of dead retinal cells and a greater number of surviving photoreceptors. Compared to controls and murine NGF treated eyes, rhNGF treated eyes showed the higher levels of intraretinal NGF and activated NGF receptors (TrkA). No differences were observed comparing eyes treated with topical and intravitreal rhNGF.
Conclusions:
In an animal model of retinitis pigmentosa NGF was effective for reducing the progression of the retinal neurodegeneration. Notably, topical administration of rhNGF seemed to be equally as effective as intravitreal rhNGF. These data suggest that a topical formulation of rhNGF could be a promising treatment for range of ocular neurodegenerative disease in which apoptosis plays a pathogenic role.
Keywords: 615 neuroprotection •
543 growth factors/growth factor receptors •
696 retinal degenerations: hereditary