Growth in foetal life, infancy, and early childhood and the association with ocular biometry.

PURPOSE: Ocular biometry varies within groups of emmetropic, hyperopic or myopic children. The aim of this study was to quantify the effect of foetal and infant growth on ocular biometry in early childhood, to determine the most important period for this association, and to examine genetic overlap with height and birth weight. METHODS: 5931 children (50.1% girls) from a population-based prospective birth cohort study underwent intra-uterine and infant growth measurements at second and third trimester, and from birth to 72 months. An ophthalmic examination including axial length (mm) and corneal radius of curvature (mm) was performed at 6 years of age. The associations between prenatal and postnatal growth variables and axial length and corneal radius of curvature were assessed with conditional linear regression analyses. Weighted genetic risk scores for birth weight and height were calculated and causality was tested with Mendelian randomisation. RESULTS: Weight and length from mid-pregnancy to 2 years of age were most important prognostic factors for axial length and corneal radius of curvature at age 4.9-9 years (mean 6.2 years S.D. 0.5). For height (Standard deviation score), the association with axial length and corneal radius of curvature was highest for the measurement at 12 months (ß 0.171 p < 0.001 and 0.070 p < 0.001). The genetic height and birth weight risk scores were both significantly associated with ocular biometry. CONCLUSIONS: Larger neonates had longer axial length and greater corneal radius of curvature. Growth during pregnancy and 2 years postnatally is the most important period underlying this association and may be partly genetically determined by genes associated with height.

Deletion of Seventeen Amino Acids at the C-Terminal End of Aquaporin 0 Causes Distortion Aberration and Cataract in the Lenses of AQP0ΔC/ΔC Mice.

Purpose: Investigate the effects of the absence of 17 amino acids at the C-terminal end of Aquaporin 0 (AQP0) on lens transparency, focusing property, and homeostasis. Methods: A knockin (KI) mouse model (AQP0ΔC/ΔC) was developed to express AQP0 only as the end-cleaved form in the lens. For this, AQP0 was genetically engineered as C-terminally end-cleaved with amino acids 1 to 246, instead of the full length 1 to 263 of the wild type (WT). After verifying the KI integration into the genome and its expression, the mouse model was bred for several generations. AQP0 KI homozygous (AQP0ΔC/ΔC) and heterozygous (AQP0+/ΔC) lenses were imaged and analyzed at different developmental stages for transparency. Correspondingly, aberrations in the lens were characterized using the standard metal grid focusing method. Data were compared with age-matched WT, AQP0 knockout (AQP0-/-), and AQP0 heterozygous (AQP0+/-) lenses. Results: AQP0ΔC/ΔC lenses were transparent throughout the embryonic development and until postnatal day 15 (P15) in contrast to age-matched AQP0-/- lenses, which developed cataract at embryonic stage itself. However, there was distortion aberration in AQP0ΔC/ΔC lens at P5; after P15, cataract began to develop and progressed faster surpassing that of age-matched AQP0-/- lenses. AQP0+/ΔC lenses were transparent even at the age of 1 year in contrast to AQP0+/- lenses; however, there was distortion aberration starting at P15. Conclusions: A specific distribution profile of intact and end-cleaved AQP0 from the outer cortex to the inner nucleus is required in the lens for establishing refractive index gradient to enable proper focusing without aberrations and for maintaining transparency.