Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. To understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol-glycosphingolipid-enriched "lipid raft" microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine-phosphorylated protein in OLs was the 120-kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand-independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX-100-insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2-FRS2 signaling in lipid rafts operates via the PI3-Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52-kd isoform of FGFR2 that lacked the extracellular ligand-binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF-dependent and -independent functions.

Mathematical models of picosecond laser keratomileusis for high myopia.

PURPOSE: Picosecond laser keratomileusis (PLK) is a refractive surgical procedure in which an intrastromal lenticle is created using the Nd:YLF picosecond laser and removed by lifting the anterior flap in the cornea. The purpose of this study was to assess the predictability of picosecond laser keratomileusis for high myopia. METHODS: The results from a recent clinical series of non-sighted patients who had undergone picosecond laser keratomileusis with the Nd:YLF picosecond laser were retrospectively simulated with two mathematical models. In one model, the change in corneal curvature resulting from the collapse of a lenticular intrastromal cavity was predicted from a geometric analysis. A second model was developed using the finite element method. The results of both predictive models were compared to the clinical results at 1 and 6 months following surgery. RESULTS: An average -13.30 D of flattening (range, -6.80 to -20.50 D) was measured at 6 months. The geometric model predicted an average correction of -23.10 D (range, -18.00 to -34.00 D), whereas the finite element model predicted an average curvature change of -17.40 D (range, -14.50 to -22.50 D). An average decrease in central pachymetry of 91 microm was measured at 6 months, as compared to a predicted decrease in thickness of 112 microm. CONCLUSIONS: The outcome of picosecond laser keratomileusis for high myopia predicted using a finite element based model shows greater change in the corneal curvature and corneal thickness compared to clinical results. The relatively thick lenticules that are removed for high myopia cause considerable deformational changes in the cornea, which preclude the use of a purely geometric/optical approach for predicting the resultant corneal curvature changes.

PRK-induced anisometropia in the rabbit as a model of myopia.

BACKGROUND: Current animal models of myopia, such as the chick and the tree shrew, have characteristics that limit their applicability to human myopia and/or their use among researchers. The purpose of this study was to establish a rabbit model of myopia based on photorefractive keratectomy (PRK)-induced anisometropia. METHODS: A group of five pigmented rabbits was treated with a monocular -5 D PRK at 5 weeks of age. At 10 weeks of age, two of the eyes were retreated with a second -5 D PRK procedure to compensate for partial regression of the refractive effect. A second group of six pigmented rabbits was treated with a monocular -6 D PRK at 10 weeks of age. Longitudinal measurements of corneal curvature, refraction, and axial length were performed until the rabbits were 13 and 21 weeks of age in groups 1 and 2, respectively. The rabbits in each group were from the same litter. RESULTS: Keratometry and retinoscopy measurements confirmed the refractive effect of the PRK procedures. At the final measurement point in group 1, the PRK-treated eyes were significantly longer than the untreated eyes (16.01 +/- 0.45 mm vs 15.45 +/- 0.56 mm). In group 2, the PRK-treated eyes were significantly longer by 0.19 mm and 0.20 mm at ages 19 and 21 weeks, respectively. CONCLUSIONS: PRK-induced anisometropia is an effective technique to induce hyperopic error compensation in the rabbit as a model of myopic development. The technique is effective if the PRK procedure is performed at either 5 or 10 weeks of age. However, after PRK at 5 weeks of age, partial retreatment may be necessary due to regression of the PRK effect.

Optical feedback controlled scleral remodeling as a mechanism for myopic eye growth.

Experimental studies of myopia have demonstrated that optical errors imposed on a developing eye will stimulate elongation of the globe, although the mechanism of axial growth is not well understood. In this study, a mathematical model of eye growth is presented in which expansion of the globe occurs as the elastic deformations of the scleral shell are incorporated into the zero stress configuration of the eye during the scleral remodeling process. The rate of remodeling is determined by the retinal blur and the amplitude of accommodation, which provide feedback loops for both unilateral and bilateral hyperopic refractive error-compensation. Normal eye growth and experimental myopia are simulated in tree shrews, a small mammal related to primates. The model demonstrates that the rate of ocular elongation in experimental myopia may be controlled by regulating the rate of soft tissue remodeling in the scleral shell.

A triphasic analysis of corneal swelling and hydration control.

Physiological studies strongly support the view that hydration control in the cornea is dependent on active ion transport at the corneal endothelium. However, the mechanism by which endothelial ion transport regulates corneal thickness has not been elaborated in detail. In this study, the corneal stroma is modeled as a triphasic material under steady-state conditions. An ion flux boundary condition is developed to represent active transport at the endothelium. The equations are solved in cylindrical coordinates for confined compression and in spherical coordinates to represent an intact cornea. The model provides a mechanism by which active ion transport at the endothelium regulates corneal hydration and provides a basis for explaining the origin of the "imbibition pressure" and stromal "swelling pressure." The model encapsulates the Donnan view of corneal swelling as well as the "pump-leak hypothesis."

Constitutive laws for biomechanical modeling of refractive surgery.

Membrane inflation tests were performed on fresh, intact human corneas using a fiber optic displacement probe to measure the apical displacements. Finite element models of each test were used to identify the material properties for four different constitutive laws commonly used to model corneal refractive surgery. Finite element models of radial keratotomy using the different best-fit constitutive laws were then compared. The results suggest that the nonlinearity in the response of the cornea is material rather than geometric, and that material nonlinearity is important for modeling refractive surgery. It was also found that linear transverse isotropy is incapable of representing the anisotropy that has been experimentally measured by others, and that a hyperelastic law is not suitable for modeling the stiffening response of the cornea.

Corneal integrity after refractive surgery. Effects of radial keratotomy and mini-radial keratotomy.

PURPOSE: Mini-radial keratotomy (mini-RK) involves limiting the extent of radial incisions to within 3.5 mm from the center of the central clear zone, compared with incisions that extend close to or beyond the limbus, as with "conventional" RK. This study was designed to determine if shorter incision length reduces the likelihood of corneal rupture after blunt trauma. METHOD: Sixteen fresh human anterior segments were divided into four groups and mounted onto an artificial anterior chamber. Four corneas with no incisions were used as controls, four received regular four-incision RK, four received four mini-RK incisions, and four received eight mini-RK incisions. Incisions extended from the 3.0-mm central clear zone to 1 mm inside the limbus (regular RK), or from the 3.0-mm central clear zone to the 7.0-mm mark (mini-RK). A pump slowly infused the artificial anterior chamber with a balanced salt solution while the pressure was continuously monitored with an electronic pressure transducer. The maximum pressure and the site of the rupture were recorded. RESULTS: Control corneas ruptured at the limbus, whereas all surgical eyes ruptured at incision sites. The corneas subjected to mini-RK ruptured at significantly higher pressures than corneas that had undergone regular RK (P < 0.01). CONCLUSION: Reducing incision length appears to reduce the likelihood of corneal rupture as intraocular pressure is increased. Mini-RK may be advantageous for patients at high risk for ocular trauma.

Supervisory status of charge nurses: Supreme Court ends controversy.

A recent Supreme Court decision has refuted the National Labor Relations Board's position that supervisory field RNs are not technically supervisors. This decision makes it easier for providers to supervise staff and aligns these nurses more closely with management.

Corneal tensile strength in fully healed radial keratotomy wounds.

PURPOSE: To investigate the susceptibility to rupture of a human donor cornea with fully healed radial keratotomy (RK) incisions using biomechanical measurement methods and finite element analysis. METHODS: A human cornea 8 years after RK was cut into four strips and subjected to tensile testing until rupture occurred. The fellow cornea was pressurized on an artificial anterior chamber beyond the initiation of wound gape. The tensile strengths of nine strips from unincised corneas were measured as controls. To investigate the effect of epithelial plugs on the RK strip test results, a finite element model of a strip containing an epithelial plug was analyzed. RESULTS: Rupture occurred along the wound site with wide variability in the measured tensile strengths. There was no significant difference in tensile strength between the RK corneal strips (16.6 +/- 4.43 N/mm2) and the control strips (19.1 +/- 3.50 N/mm2). Four of the eight incisions of the fellow RK cornea gaped, but the cornea did not rupture up to a pressure of 2740 mm Hg. An epithelial plug of 10% of the corneal thickness was found in one of the incisions. The finite element results demonstrated higher stresses at the wound site that increased with the size of the epithelial plug. CONCLUSIONS: The presence of an epithelial plug in a fully healed radial keratotomy incision will create a stress concentration at the incision site that may predispose the cornea to rupture. The variability in the strength measurements indicates that the increase in rupture susceptibility due to RK may be hard to predict and may depend on factors such as the size of the plug and the strength of the wound collagen.