Refractive, visual, and subjective quality of vision outcomes for very high myopia LASIK from - 10.00 to - 13.50 diopters.

BACKGROUND: To evaluate laser-assisted in situ keratomileusis (LASIK) outcomes, subjective quality of vision (QoV) and patient satisfaction in eyes with very high myopia (VHM) above - 10.00 diopters (D). METHODS: Consecutive myopic and myopic-astigmatism eyes with spherical equivalent (SEQ) ranging between - 10.00 to - 13.50 D underwent LASIK with the WaveLight® Allegretto Wave® Eye-Q 400 Hz excimer laser. Treatment accuracy, efficacy, safety, stability, cylinder vectors, and higher-order aberrations were evaluated, together with subjective QoV and night vision disturbances (NVDs). RESULTS: 114 eyes had a preoperative SEQ of - 11.02 ± 0.81 D, with a median follow-up of 24 months. A total of 72, 84, and 94% of eyes were within ± 0.50, ± 0.75 and ± 1.00 D of intended SEQ (R2 = 0.71). The efficacy index was 0.93 ± 0.20, with 51 and 81% of eyes achieving 20/20 and 20/25. The astigmatism correction index was 0.95 ± 0.33. The safety index was 1.05 ± 0.12. The average myopic regression was - 0.51 ± 0.38 D. Preoperative QoV scores improved significantly postoperatively (7.5 ± 0.8 vs. 9.1 ± 0.7; P <  0.001), with less NVDs (P <  0.001). Total, spherical and coma root mean square (RMS) postoperative ocular higher-order aberrations were 1.07 ± 0.34, 0.67 ± 0.25, and 0.70 ± 0.40 µm. CONCLUSIONS: Very high myopia LASIK between - 10.00 to - 13.50 D is safe and results in good visual outcomes, with high patient satisfaction and a significant improvement in patient-reported QoV after surgery. Appropriately selected patients within this very high myopia group can be included as LASIK candidates.

RGMB and neogenin control cell differentiation in the developing olfactory epithelium.

Cellular interactions are key for the differentiation of distinct cell types within developing epithelia, yet the molecular mechanisms engaged in these interactions remain poorly understood. In the developing olfactory epithelium (OE), neural stem/progenitor cells give rise to odorant-detecting olfactory receptor neurons (ORNs) and glial-like sustentacular (SUS) cells. Here, we show in mice that the transmembrane receptor neogenin (NEO1) and its membrane-bound ligand RGMB control the balance of neurons and glial cells produced in the OE. In this layered epithelium, neogenin is expressed in progenitor cells, while RGMB is restricted to adjacent newly born ORNs. Ablation of Rgmb via gene-targeting increases the number of dividing progenitor cells in the OE and leads to supernumerary SUS cells. Neogenin loss-of-function phenocopies these effects observed in Rgmb(-/-) mice, supporting the proposal that RGMB-neogenin signaling regulates progenitor cell numbers and SUS cell production. Interestingly, Neo1(-/-) mice also exhibit increased apoptosis of ORNs, implicating additional ligands in the neogenin-dependent survival of ORNs. Thus, our results indicate that RGMB-neogenin-mediated cell-cell interactions between newly born neurons and progenitor cells control the ratio of glia and neurons produced in the OE.

Cellular and molecular mechanisms regulating embryonic neurogenesis in the rodent olfactory epithelium.

Mechanisms that regulate cellular differentiation in developing embryos are maintained across multiple physiological systems, including the nervous system where neurons and glia are generated. The olfactory epithelium, which arises from the olfactory pit, is a stratified tissue in which the stepwise generation of neurons and support cells can easily be assessed and followed during embryogenesis and throughout adulthood. During olfactory epithelium morphogenesis, progenitor cells respond to factors that control their proliferation, survival, and differentiation in order to generate olfactory receptor neurons that detect odorants in the environment and glia-like sustentacular cells. The tight temporal regulation of expression of proneural genes in dividing progenitor cells, including Mash-1, Neurogenin-1, and NeuroD1, plays a central role in the production of olfactory receptor neurons. Multiple factors that either positively or negatively affect the generation of olfactory receptor neurons have been identified and shown to impinge on the transcriptional regulatory network in dividing progenitor cells. Several growth factors, such as FGF-8, act to promote neurogenesis by ensuring survival of progenitor cells that will give rise to olfactory receptor neurons. In contrast, other molecules, including members of the large TGF-ß family of proteins, have negative impacts on neurogenesis by restricting progenitor cell proliferation and stalling their differentiation. Since recent reviews have focused on neurogenesis in the regenerating adult olfactory epithelium, this review describes neurogenesis at embryonic stages of olfactory epithelium development and summarizes our current understanding of how both cell intrinsic and extrinsic factors control this process.

Neogenin may functionally substitute for Dcc in chicken.

Dcc is the key receptor that mediates attractive responses of axonal growth cones to netrins, a family of axon guidance cues used throughout evolution. However, a Dcc homolog has not yet been identified in the chicken genome, raising the possibility that Dcc is not present in avians. Here we show that the closely related family member neogenin may functionally substitute for Dcc in the developing chicken spinal cord. The expression pattern of chicken neogenin in the developing spinal cord is a composite of the distribution patterns of both rodent Dcc and neogenin. Moreover, whereas the loss of mouse neogenin has no effect on the trajectory of commissural axons, removing chicken neogenin by RNA interference results in a phenotype similar to the functional inactivation of Dcc in mouse. Taken together, these data suggest that the chick neogenin is functionally equivalent to rodent Dcc.