Abstract
Purpose :
Prenatal exposure to drugs is a worldwide growing problem. Research into the impact of marijuana use during pregnancy has focused primarily on brain development and cognitive outcomes in the offspring. Besides its localization, the retina is part of the central nervous system, however little is known about the impacts maternal cannabis use on retina development and its potential postnatal consequences. We hypothesized that recreational use of marijuana during pregnancy alters retina structure in the offspring and changes are age-dependent. To test this we developed a murine model that mimics human exposures in terms of dose and use.
Methods :
This study was approved by the Ethics Committee of the University of São Paulo. Pregnant BalbC mice were exposed (nose-only) daily during 5min to either marijuana smoke [0.2g of Cannabis] or filtered air from gestational day 5 to18 (n=10/group). Outside exposure period, animals were kept in ventilated cage system with food and water ad libitum (Temp=21oC, 12/12-h light/dark cycle). After weaning period, male and female pups were separated and weekly clinically examined. At 3, 6 and 12 months of age, 5 females and 5 males were randomly selected from each group for SD-OCT analysis of the retina. During the exams, mice were anesthetized by subcutaneous injection of ketamine and xylazine, pupils dilated with tropicamide eye drops. Retina layers were measured (NFL+RGCL, IPL, INL, OPL, IS/OS, RPE) and the inner, outer and total retina thickness calculated. Means and SEM were calculated and a MANOVA were performed to resolve the main effects of gestational exposure, gender, age and to check if there are interaction effects. Null hypotheses were rejected at a probability level of P= 0.05.
Results :
Our data show that the retina of animals exposed prenatally to marijuana are thinner (p=0.02, less 12%), this is due to significant reduction in the inner retina (p=0.015). There are an interaction effect of age and exposure for these outcomes. This suggests that as animals get older the retina becomes thinner. Detailed examination of the inner retina layers reveals that the thickness of INL are significantly reduced, age and exposure are the determinant factors (p=0.007).
Conclusions :
In summary, we have shown for the first time that gestational exposure to marijuana smoke may have lasting effects on the structure of the retina and these alterations seem to progress with age.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.