Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye.

Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a threefold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty, we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft.

Profilin-1 downregulation has contrasting effects on early vs late steps of breast cancer metastasis.

Profilin1 (Pfn1), a ubiquitously expressed actin-binding protein, has an indispensable role in migration and proliferation of normal cells. Seemingly contrary to its essential cellular functions, Pfn1's expression is downregulated in breast cancer, the significance of which is unclear. In this study, expression profiling of Pfn1 in human breast cancer specimens correlates lower Pfn1 expression levels with propensity to metastasize. Xenograft experiments further establish a causal relationship between loss of Pfn1 expression and increased dissemination of breast cancer cells (BCCs) from the primary mammary tumor. BCCs exhibit a hyperinvasive phenotype (marked by matrix metalloproteinase-9 upregulation, faster invasion through collagen matrix) and acquire increased proficiency to transmigrate through endothelial barrier (an obligatory step for vascular dissemination) when Pfn1 expression is suppressed. In Pfn1-deficient cells, hyperinvasiveness involves a phosphatidylinositol 3-kinase-PI(3,4)P2 signaling axis while augmented transendothelial migration occurs in a vascular endothelial growth factor-dependent manner. Contrasting these dissemination promoting activities, loss of Pfn1, however, dramatically inhibits metastatic outgrowth of disseminated BCCs, suggesting that Pfn1 has a key role in the metastatic colonization process. In summary, this study shows that Pfn1 has a dichotomous role in early vs late steps of breast cancer metastasis.

Surgically induced astigmatism after hyperopic and myopic photorefractive keratectomy.

PURPOSE: To compare the axis and magnitude of surgically induced refractive astigmatism (SIA) after hyperopic and myopic photorefractive keratectomy (PRK). SETTING: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. METHODS: In this single-center retrospective study, the VISX Star S2 excimer laser was used to create a peripheral annular ablation profile to correct spherical hyperopia in 23 eyes of 16 consecutive patients. Attempted corrections ranged from +0.50 diopter (D) to +4.25 D with 0 to 1.00 D of astigmatism. The same laser was used to create a central ablation profile to correct spherical myopia in 25 eyes of 17 consecutive patients. Attempted corrections ranged from -2.25 to -6.50 D with 0 to 1.00 D of astigmatism. The absolute change in refractive astigmatism was calculated by taking the difference in magnitudes of astigmatism before and after laser treatment without regard to axis. Axis and magnitude of SIA were analyzed by vector differences. Magnitudes were compared using the Student t test, and axial shifts were compared using the chi-square test. All patients were followed for a minimum of 6 months. RESULTS: The mean changes in absolute astigmatism were 0.29 +/- 0.28 D at 3 months and 0.34 +/- 0.29 D at 6 months after hyperopic PRK and 0.40 +/- 0.35 D at 3 months and 0.39 +/- 0.36 D at 6 months after myopic PRK. The mean vectoral magnitudes were 0.49 +/- 0.29 at 3 months and 0.52 +/- 0.25 at 6 months after hyperopic PRK and 0.48 +/- 0.39 at 3 months and 0.44 +/- 0.38 at 6 months after myopic PRK. The mean values for SIA (the centroid) were 0.10 +/- 0.57 D x 113 degrees at 3 months and 0.15 +/- 0.57 D x 131 degrees at 6 months after hyperopic PRK and 0.04 +/- 0.63 D x 160 degrees at 3 months and 0.08 +/- 0.58 D x 171 degrees at 6 months after myopic PRK. There was no statistically significant difference between the 2 groups in vectoral axis or magnitude of SIA. CONCLUSION: Surgically induced astigmatism after hyperopic PRK was comparable to astigmatism induced by myopic PRK. A peripheral annular ablation for hyperopic correction, similar to a central ablation in myopic PRK, did not appear to result in uneven corneal healing causing astigmatism.

The application of in vivo confocal microscopy and tear LDH measurement in assessing corneal response to contact lens and contact lens solutions.

PURPOSE: To evaluate differences in corneal response to daily wear (DW) of soft contact lens (CL) wear with different CL solutions and to assess the ability of in vivo confocal microscopy (CM) and tear lactate dehydrogenase (LDH) measurement to detect such differences in NZW rabbits. METHODS: Daily treatment of lenses consisted of a rub and rinse cleaning, then overnight soak in one of five solutions: Sauflon All in One (ALL), Compound A (CoA), OPTI-FREE((R) )Rinsing, Disinfecting, and Storage Solution (OPT), ReNu((R)) Multipurpose Solution (REN), and UNISOL( (R)) Saline Solution (UNI). Rabbits (4/test group) wore 71% H( 2)O/type4 soft lenses approximately 7 hours daily. On days 0, 1, 3 and 7, slit lamp examination, tear LDH measurement, and in vivo CM were performed after removal of lenses. Using in vivo CM, epithelial thickness, epithelial cell area, and stromal thickness were measured, both centrally and peripherally. RESULTS: Epithelial thickness in ALL, CoA, and UNI-treated eyes showed a significant decrease of 15.6%, 13. 3%, and 10.6% (p < 0.05 in all groups), centrally, while CoA, OPT, and UNI showed a significant decrease of 9.3%, 7.1%, and 4.4% (p < 0. 05 in all groups), peripherally. ALL showed a significant 9.5% (p < 0.05) decrease of central cell area, while CoA showed a significant 21.5% (p < 0.01) decrease peripherally. UNI demonstrated a significant 3.2% (p < 0.05) decrease in central stromal thickness. ALL, CoA, and UNI showed a significant increase in LDH level of 152. 1%, 192.1%, and 308.2% (p < 0.05 in all groups) at day 3, respectively, but values declined at day 7. Significant changes in basal epithelial morphology were also observed with CoA on day 7 on in vivo CM. CONCLUSIONS: Overall, lens care solutions in combination with CL wear may interact to cause increased epithelial desquamation leading to decreased surface cell area and epithelial thickness. The clinical significance of these changes will require further investigation. In vivo CM combined with tear LDH assay is a quantitative, objective, non-invasive method of assessing CL wear and CL disinfecting solution effects on the cornea, and is able to detect differences in corneal response to different CL solutions.

Ocular water evaporation and the dry eye. A new measuring device.

We developed a simple device to measure the water evaporation from the ocular surface, and we measured the evaporation rate in 18 normal individuals. We compared this to a group of 15 patients with dry eye from low tear production. We found the normal rate of water evaporation from the ocular surface to be 14.7 +/- 6.4 x 10(-7) g/cm2/s or 0.14 +/- 0.06 microliter/min at 30% relative humidity. For dry eye patients, the rate was significantly increased to 47.6 +/- 20.1 x 10(-7) g/cm2/s or 0.43 +/- 0.19 microliter/min (p < 0.005). Neither group showed any evidence of meibomian gland dysfunction that might have increased evaporation. From these results, we conclude that evaporation is accelerated when tear production decreases and is of sufficient magnitude to exacerbate the dry eye.

Morphologic effects of contact lens wear on the corneal surface.

We used specular microscopy of the corneal epithelium to examine 29 eyes of 29 patients each wearing one of five different types of contact lenses. We compared these with 24 eyes of 24 age-matched control patients. We found patients with aphakic extended wear soft contact lenses had significantly larger cells (818 +/- 186 microns2) than all other groups; and they were significantly larger than their age-matched control group (573 +/- 174 microns2) (P less than .002). The epithelial cells of extended wear soft contact lens patients (609 +/- 97 microns2) and daily wear rigid gas permeable contact lens patients (613 +/- 103 microns2) were larger than their control group of normal young patients (513 +/- 53 microns2). The cells of daily wear soft contact lens patients (484 +/- 111 microns2) and hard contact lens patients (517 +/- 46 microns2), however, were not different from controls. This study demonstrates a statistically significant shift in mean cell area of corneal epithelial cells in patients wearing some types of contact lenses.