Abstract
PurposeThe purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period.MethodsSixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2’5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0.ResultsSlit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl.ConclusionsOur results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.
Highlights
IntroductionPolyunsaturated fatty acids (PUFAs) are essential molecules required from de diet, which are classified by the position of the first double bound counting from the metil-terminal in omega-3 third carbon- (eicosapentaenoic acid, docosahexaenoic acid and alinolenic acid) and omega-6 -sixth carbon- (linoleic acid and arachidonic acid)
Polyunsaturated fatty acids (PUFAs) are essential molecules required from de diet, which are classified by the position of the first double bound counting from the metil-terminal in omega-3 third carbon- and omega-6 -sixth carbon
Concentrations of docosahexaenoic acid (DHA) used in groups 2, 3 and 4 (2’5 mg/50 ml, 5 mg/50 ml and 10 mg/50 ml respectively) were considered clinically unsafe
Summary
Polyunsaturated fatty acids (PUFAs) are essential molecules required from de diet, which are classified by the position of the first double bound counting from the metil-terminal in omega-3 third carbon- (eicosapentaenoic acid, docosahexaenoic acid and alinolenic acid) and omega-6 -sixth carbon- (linoleic acid and arachidonic acid). The most important omega-3 fatty acid in the nervous system and the retina is docosahexaenoic acid (DHA), highly concentrated in the outer segments of photoreceptors and synaptic membranes. DHA plays a key role in cellular integrity, development and function [1] and it is an essential structural component of cellular membranes. It shows a functional role, as the proper rhodopsin functionality and visual transduction depend on the adequate proportion of DHA within the retinal cell membranes phospholipids. [3] These effects can result from independent mechanisms such as: membrane functional integrity amelioration, recruitment and up-regulation of anti-apoptotic molecules (as the members of the Bcl-2 gene family) or down-regulation of proapoptotic signals, regression or suppression of inflammatory mediators.
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