Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension.
BACKGROUND
It has been shown that intravitreal injection of NGF inhibits ganglion cell degeneration after optic nerve transection and ischemic injury. The aim of our study was to investigate the presence of NGF in aqueous humor and its involvement in retinal damage during ocular hypertension.


METHODS
We used an experimental model of ocular hypertension in rabbit. Before treatment and 4, 10 and 15 days after induction of hypertension, we evaluated histological retinal damage and NGF levels in aqueous humor using an immunoenzymatic assay. Polyclonal anti-NGF antibodies were injected intravitreally into one eye of each rabbit (n = 6), and the animals were killed after 4 days of hypertension. Another group of rabbits (n = 12) was injected retro-ocularly with NGF and killed after 10 or 15 days of treatment for histologic evaluation of the retina.


RESULTS
Our data show that experimental ocular hypertension in adult rabbits induces retinal damage and enhances local NGF levels. The highest NGF value was found after 4 days of intraocular hypertension: high levels persisted, though to a lesser extent, for up to 15 days. Histological examination revealed that the number of retinal ganglion cells (RGC) remained unchanged during the first 4 days but decreased at 10 days. These studies also showed that retro-ocular administration of NGF reduced RGC loss, whereas intraocular injection of NGF antibodies, which inhibited the endogenous NGF, exacerbated the retinal insult.


CONCLUSIONS
These findings demonstrate a protective effect of NGF on RGC damaged by ocular hypertension and prompt further investigations to evaluate a possible therapeutic use of NGF to retard RGC death in humans.
Lambiase
A
A
CNR, Institute of Neurobiology, Rome, Italy.
Centofanti
M
M
Micera
A
A
Manni
G L
GL
Mattei
E
E
De Gregorio
A
A
de Feo
G
G
Bucci
M G
MG
Aloe
L
L
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000008:administration & dosage; D008297:Male; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009798:Ocular Hypertension / Q000150:complications*; D011817:Rabbits; D012164:Retinal Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D014822:Vitreous Body
D007074:Immunoglobulin G; D009414:Nerve Growth Factors