B3645 - Is there a causal association between insulin signalling and myopia pathogenesis - 11/11/2020

B number: 
Principal applicant name: 
Denize Atan | University of Bristol
Mr Max Gillies
Title of project: 
Is there a causal association between insulin signalling and myopia pathogenesis?
Proposal summary: 

Myopia, or short-sightedness, is one of the most common causes of sight impairment worldwide. By 2050, five billion people- half the world’s population- will be short-sighted, compared to ~1.4 billion people today.
People with myopia have relatively long eyes, so that light is focused in front of the retina instead of directly onto it. Since the eye continues to grow throughout childhood, someone who develops myopia as a child will continue to get worse as they grow older, with greater risk of sight-threatening complications.
Previously, we showed that for each additional year we spend in education, the more myopic we become, on average, as a population. Evidence from other studies suggests that this may be because we spend less time outside, reducing our exposure to natural daylight. Other risk factors for myopia include the time we spend on near work, urbanization, socioeconomic position, diet, pregnancy-related factors and genetics. Children with myopia tend to engage in less physical activity, but physical activity alone is not protective against myopia.
Myopia is more prevalent in countries adopting a Western diet and lifestyle, and many of the genes that increase the risk of myopia are involved in insulin/glucose signalling and obesity/fat metabolism. Insulin signalling also appears to influence the normal growth of the eye. As the Western diet is linked to greater intake of food with higher energy loads, one hypothesis is that compensatory increases in blood glucose and insulin levels send increased growth signals to the eyes.
This project aims to determine how genetic and environmental factors interact with insulin signalling to affect myopia. Changes in insulin signalling happen naturally in children around puberty, and so we would like to use information in the Avon Longitudinal Study of Parents and Children on eye growth, glasses prescriptions, blood levels of glucose and insulin before, during and after puberty on thousands of children followed prospectively from birth, to find out how they interact to affect eye growth. Additionally, there are normal variants in our genes that influence fasting levels of insulin and glucose and we will find out how these genetic variants are linked to myopia. These analyses should provide novel insights into the relationship between insulin signalling and myopia, and have the potential to identify novel targets for treatment.

Impact of research: 
The above analyses will help us determine whether genetic and environmental changes in insulin/IGF1 signalling are major determinants of axial growth in children and myopia pathogenesis. If so, they would explain how myopia is linked to increasing urbanisation, diet, BMI, height and PHV during puberty, and why GWAS and studies of animal models of myopia implicate insulin/IGF pathways. They might also point the way to novel therapies for myopia that target downstream effector molecules in the insulin/IGF1 signalling pathway, e.g. PI3K/AKT. The efficacy of topical atropine eye drops for myopia suggests that local or topical delivery routes could be an option
Date proposal received: 
Wednesday, 28 October, 2020
Date proposal approved: 
Friday, 30 October, 2020
Genetic epidemiology (including association studies and mendelian randomisation), Diabetes, GWAS, Statistical methods, Ageing, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Nutrition - breast feeding, diet, Puberty, Statistical methods, Vision, BMI, Childhood - childcare, childhood adversity, Epigenetics, Genetic epidemiology, Genetics, Genome wide association study, Hormones - cortisol, IGF, thyroid, Mendelian randomisation