June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Prenatal exposure to marijuana causes morphological retinal changes in mice
Author Affiliations & Notes
  • paulo zantut
    University of Sao Paulo Medical School, Brazil
  • Mariana Veras
    University of Sao Paulo Medical School, Brazil
  • Walter Takahashi
    University of Sao Paulo Medical School, Brazil
  • Sarah Benevenuto
    University of Sao Paulo Medical School, Brazil
  • Angelica Safatle
    university of sao paulo, Brazil
  • ricardo pecora
    university of sao paulo, Brazil
  • Paulo Saldiva
    University of Sao Paulo Medical School, Brazil
  • Francisco Max Damico
    University of Sao Paulo Medical School, Brazil
  • Footnotes
    Commercial Relationships   paulo zantut, None; Mariana Veras, None; Walter Takahashi, None; Sarah Benevenuto, None; Angelica Safatle, None; ricardo pecora, None; Paulo Saldiva, None; Francisco Max Damico, None
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4282. doi:
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      paulo zantut, Mariana Veras, Walter Takahashi, Sarah Benevenuto, Angelica Safatle, ricardo pecora, Paulo Saldiva, Francisco Max Damico; Prenatal exposure to marijuana causes morphological retinal changes in mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4282.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Prenatal exposure to marijuana is a worldwide growing problem. Although retina is part of the central nervous system, little is known about the impacts of maternal cannabis use on the retinal development and its potential postnatal consequences. Considering that the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of marijuana during pregnancy alters 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 (nose-only) daily for 5 min to either marijuana smoke [0.2 g of Cannabis] or filtered air from gestational day 5 to18 (n=10/group). After weaning period, pups were separated and weekly examined. At 2, 4, 6 and 12 months of age, 10 pups from each group were selected for SD-OCT analysis of the retina. Retina layers were measured (NFL+RGCL, IPL, INL, OPL, IS/OS, RPE) and the inner, outer and total retina thickness were calculated. Fifty seven mice of both groups were sacrificed on days 20, 60, and 360 for retinal stereology (fractionary volume of the retinal layers, volume of each retinal layer and of the total volume of retina) and light microscopy. Means and SEM were calculated and MANOVA was performed. Null hypotheses were rejected at a probability level of P= 0.05.

Results :
Our data show that the retina of animals prenatally exposed to marijuana is 17% thinner on month 4 than controls (p=0.005) due to significant reduction of the outer retina (p=0.001). The analysis of each retinal layer showed that mice of the exposed group presented thickening of the IS/OS in comparison to controls (p<0.001). In the volumetric analyses by retinal stereology, the exposed mice presented an 89% increase of the IS/OS on month 2 compared to controls (p=0.001) and normalization on month 12 (p=0.001). Light microscopy showed that exposed mice presented 64% thickening of the IS/OS on month 12 compared to controls (p=0.041).

Conclusions : We have shown for the first time that gestational exposure to marijuana smoke may cause structural changes in the retina of the offspring that continue even with the aging of the mouse. These are experimental evidences that suggest that children and young adults born from mothers who used to smoke marijuana during pregnancy may require clinical care earlier and more frequent than the non-exposed population.

This is a 2020 ARVO Annual Meeting abstract.

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