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M. P. Feldkaemper, F. Schaeffel; Insulin Inhibits Compensation of Plus Lenses in Chicks and Stimulates Myopia Development. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5924.
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In recent studies it was speculated that refractive errors might be associated with a metabolic disturbance in the blood sugar level. Moreover, it was found that glucagon might act as a stop signal for eye growth, at least in chicks. Since glucagon and insulin have opposite effects on blood glucose levels, we investigated the influence of insulin on eye growth in untreated and plus lens treated chicks.
Male white leghorn chicks, aged 7 days, were intravitreally injected every second day with insulin (0.1 U, 0.01 U and 0.001 U respectively). In addition they were either bilaterally treated with +7D lenses (group A) or did not wear lenses (group B). Additional control groups were injected with saline and bilaterally treated with +7D lenses (group C) or without lenses (group D). Four days after the injections, refraction was measured by infrared photoretinoscopy and axial length was determined by A-scan ultrasound. The short term influence of insulin on ZENK mRNA levels, a transcription factor with potential relevance for eye growth regulation, was quantified after one hour of plus lens wear and an injection of 0.01 U insulin using real-time RT-PCR.
In plus lens treated chicks, insulin injections (0.1 U, 0.01 U) significantly increased axial eye growth and lens thickness, compared to saline injected animals (group A vs. group C: 0.1 U insulin: delta axial lenght:0.95 vs. 0.06 mm, delta lens thickness: 0.47 vs. 0.14 mm, p < 0.001). Insulin did not only prevent plus lens compensation, but even induced high myopia (e.g. group A 0.01 U insulin, delta refraction day 0 to day 4: -8.6 ±; 1.8D). The effects of insulin on ocular dimensions and refractive development were reversible. If the chicks were allowed to recover, axial length, lens thickness and refraction returned to normal values within 5 days. Insulin injections (0.1 U) in otherwise untreated animals (group B) stimulated axial eye growth compared to control animals that received saline injections (delta axial length: 0.52 ±; 0.02 mm vs. 0.31 ±; 0.04 mm). One hour after intravitreal injection of insulin (0.01 U ) in plus lens treated chicks, ZENK mRNA levels were significantly increased by 284%, compared to saline injected plus lens treated animals.
Insulin induces excessive axial eye growth and myopia, as well as swelling of the crystalline lens. Thereby, it suppresses compensation of plus lens defocus. Moreover, insulin injections increase Egr-1 mRNA levels in retinal cells, an effect that is normally associated with a stop signal for eye growth. That intravitreal insulin is strongly myopigenic in the chick model is very unexpected and requires further studies.
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