ABSTRACT
BACKGROUND: Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. METHODS: Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. RESULTS: The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). CONCLUSION: Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.
ABSTRACT
Purpose: To determine the prevalence of focal inner, middle, and combined inner/middle retinal thinning (FIRT, FMRT, and FCRT, respectively) in different stages of diabetic retinopathy (DR) without diabetic macular edema and to assess the relationship between such findings with ocular and systemic parameters. Methods: This was a cross-sectional, comparative study comprising healthy participants and diabetic patients with different stages of DR. Forty-nine horizontal macular B-scans from the selected eye were obtained using spectral-domain optical coherence tomography (SD-OCT) and analyzed for the presence of FIRT, FMRT, or FCRT and any relationship with systemic and ocular parameters. Focal retinal thinning (FRT) was subjectively defined as any evidence of inner and/or middle retinal thinning. Results: A total of 190 participants (52 healthy participants and 138 diabetic patients) were included. A higher prevalence of FRT was observed in eyes with advanced DR versus healthy eyes and versus diabetic eyes with no DR or mild DR. FIRT and FCRT were significantly greater in eyes with proliferative DR treated with pan-retinal photocoagulation, and FMRT was significantly more common in eyes with severe nonproliferative DR. FRT was significantly more common in patients with coronary artery disease and was positively correlated with diabetes duration, serum creatinine, and glycosylated hemoglobin and negatively correlated with age, estimated glomerular filtration rate, and visual acuity. Conclusions: FRT occurs in all stages of DR and is increasingly prevalent with increasing severity of DR. Translational Relevance: OCT identification of FRT may provide a surrogate biomarker of retinal and systemic disease in diabetic patients.
