Squalamine lactate reduces choroidal neovascularization in a laser-injury model in the rat.
OBJECTIVE
To determine if systemically administered squalamine lactate, a novel aminosterol with antineoplastic and antiangiogenic activity, inhibits the development of experimental choroidal neovascularization membranes (CNVMs) induced by laser trauma in a rat model.


METHODS
Twenty anesthetized male Brown-Norway rats received a series of 8 krypton red laser lesions per eye (647 nm, 0.05 second, 50 microm, 150 mW). One half the animals received an intraperitoneal injection of squalamine and the other one half received an injection of 5% dextrose in water, all performed in a masked fashion. Fundus photography and fluorescein angiography were performed at postlaser treatment days 14 and 28, and ocular tissues were processed for light microscopic examination following euthanasia of the rats on postlaser treatment day 28.


RESULTS
Although fundus photography and fluorescein angiography yielded no statistically significant quantitative differences between the two groups, histologic analysis of the lesion sites revealed a partial but statistically significant reduction of experimental CNVM development in the squalamine-treated population. In particular, the squalamine-treated eyes (n = 20) demonstrated lesions (n = 149) with a mean CNVM thickness +/- SD of 47 +/- 11 microm, as compared with the control eyes (n = 20) that had lesions (n = 142) with a mean CNVM thickness +/- SD of 63 +/- 14 microm (P < 0.001).


CONCLUSIONS
Systemically administered squalamine lactate partially reduced choroidal neovascular membrane development induced by laser trauma in this animal model. In conjunction with other existing and developing therapies, this agent may have a potential role in the treatment of human CNVM formation. Further study of squalamine lactate for treatment of neovascular eye disease is warranted.
Ciulla
Thomas A
TA
Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. thomasciulla@yahoo.com
Criswell
Mark H
MH
Danis
Ronald P
RP
Williams
Jon I
JI
McLane
Michael P
MP
Holroyd
Kenneth J
KJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002777:Cholestanols / Q000627:therapeutic use*; D002829:Choroid / Q000293:injuries; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D007274:Injections, Intraperitoneal; D017075:Laser Coagulation / Q000009:adverse effects; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D002777:Cholestanols; C079655:squalamine