EphA2 Affects Development of the Eye Lens Nucleus and the Gradient of Refractive Index.

Purpose: Our studies in mouse eye lenses demonstrate that ephrin-A5 and EphA2 are needed for normal epithelial cells and lens transparency. We sought to determine whether EphA2 and ephrin-A5 are important for lens morphometrics, nucleus formation, and refractive index. Methods: We performed tissue morphometric measurements, electron microscopy, Western blots, and interferometric measurements using an X-ray synchrotron beam source to measure the gradient of refractive index (GRIN) to compare mouse lenses with genetic disruption of EphA2 or ephrin-A5. Results: Morphometric analysis revealed that although there is no change in the overall lens volume, there is a change in lens shape in both EphA2-/- lenses and ephrin-A5-/- lenses. Surprisingly, EphA2-/- lenses had small and soft lens nuclei different from hard lens nuclei of control lenses. SEM images revealed changes in cell morphology of EphA2-/- fiber cells close to the center of the lens. Inner EphA2-/- lens fibers had more pronounced tongue-and-groove interdigitations and formed globular membrane morphology only in the deepest layers of the lens nucleus. We did not observe nuclear defects in ephrin-A5-/- lenses. There was an overall decrease in magnitude of refractive index across EphA2-/- lenses, which is most pronounced in the nucleus. Conclusions: This work reveals that Eph-ephrin signaling plays a role in fiber cell maturation, nuclear compaction, and lens shape. Loss of EphA2 disrupts the nuclear compaction resulting in a small lens nucleus. Our data suggest that Eph-ephrin signaling may be required for fiber cell membrane reorganization and compaction and for establishing a normal GRIN.

Comparison of two popular nuclear disassembly techniques for cataract surgeons in training: divide and conquer versus stop and chop.

PURPOSE: To compare two common phacoemulsification techniques in the learning curve phase, and their effect on ultrasound energy dissipation. METHODS: One hundred and ten consecutive patients scheduled for cataract surgery with the same surgeon in training were prospectively enrolled. Study was divided in two parts. In the first one, 60 patients were stratified for cataract grade [nuclear opalescence (NO) grade 2-4] and divided in two groups receiving surgery with the divide-and-conquer technique (Group-1) and with the stop-and-chop technique (Group-2). In the second part, 50 patients were stratified according to cataract grade (NO2-6), and the surgeon had to choose one of the two techniques according to personal preference. The primary outcome was the cumulative dissipated energy (CDE). RESULTS: Significant differences of CDE were observed between the NO3 and NO4 cataracts in Group-1. In Group-2, this difference was not significant, suggesting that with more advanced cataracts, the stop-and-chop technique allows less ultrasound use. In the second part of the study, the stop and chop was most frequently used for more advanced cataracts. When considering harder cataracts (NO5-NO6), patients receiving surgery with the divide-and-conquer technique had higher CDE values compared to stop and chop. CONCLUSIONS: Both divide-and-conquer and stop-and-chop techniques are efficient in the learning curve. Stop and chop dissipates less energy in harder nuclei. Once surgeons reach sufficient experience with both techniques, they should switch to a stop-and-chop technique, allowing lower levels of ultrasound energy.

On the contribution of the nucleus and cortex to human lens shape and size.

BACKGROUND: The shape of the human lens changes from almost spherical at birth to ellipsoid due to a decrease in sagittal thickness and an increase in equatorial diameter during the first two decades of life. Both dimensions increase thereafter. This study was undertaken to determine the reason for the change. METHODS: Published refractive index gradients, from 20 lenses aged from seven to 82 years, were used to calculate the protein contents of concentric shells of fibre cells in human lenses. The boundaries of nuclear cores containing from 2.5 to 45 mg, in 2.5 mg increments, were determined from the isoindicial shells. Cortex thickness was determined from the distance between the 30 mg nuclear boundary and the capsule. RESULTS: The sagittal thickness of every nuclear core decreased until age 40 years and remained constant thereafter. Over the same time frame, the equatorial diameter of the cores containing up to 30 mg of protein increased, while those of cores larger than 30 mg decreased. The volumes of the cores decreased and their shapes changed from near spherical to spheroidal. Equatorial and sagittal cortex thickness increased linearly with age at 0.0082 mm per year. The anterior sagittal cortex was 0.23 mm larger than the posterior and the equatorial cortex was 0.62 mm greater. CONCLUSIONS: Changes in lens shape observed during the first two decades of life are due to remodelling and compaction of the 30 mg nuclear core. Cortex growth is linear throughout life.

Aging of the human lens: changes in lens shape at zero-diopter accommodation.

Scheimpflug photographs of the zero-diopter-accommodated anterior segments of 100 human subjects, aged 18 to 70 yr and evenly spaced over this range, were digitized and analyzed to characterize lens and lens nucleus shape as a function of age by the Hough transform and other image analysis methods. Anterior and posterior lens surface curves exhibit a decrease in radius of curvature with increasing age, in qualitative but not quantitative agreement with the earlier observations of Brown [Exp. Eye Res. 19, 175 (1974)]. In contrast, the shape of the lens nuclear boundaries changes little with age. Overall lens volume at zero diopters increases with age, but the volume of the lens nucleus remains unchanged. The lens center of mass moves anteriorly with increasing age, as does the central clear region of the lens. Although these data sets were found to be more variable than those of Brown, the complementary variability of other factors, such as anterior chamber depth, for each subject leads to a very high statistical correlation between lens shape and lens location relative to the cornea. This supports the finding of previous work that image formation on the retina for a given individual results from the multifactorial balancing of related factors.