| The pathophysiology of Acanthamoeba keratitis Trends in Parasitology, Volume 22, Issue 4, 1 April 2006, Pages 175-180 Daniel W. Clarke and Jerry Y. Niederkorn Abstract keratitis is a sight-threatening infection of the ocular surface that is produced by several free-living amebae of the genus . Infection is usually initiated by -contaminated contact lenses and produces exquisite pain and ulceration of the ocular surface. The pathophysiology of this infection involves an intricate series of sequential events that includes the production of several pathogenic proteases that degrade basement membranes and induce cytolysis and apoptosis of the cellular elements of the cornea, culminating in dissolution of the collagenous corneal stroma. Targeting such proteases could lead to the development of vaccines that target the disease process rather than the pathogen itself. Abstract | Full Text | PDF (307 kb) |
| Ocular gene therapy: current progress and future prospects Trends in Molecular Medicine, Volume , Issue , 18 December 2008, Pages Pasqualina Colella, Gabriella Cotugno and Alberto Auricchio Abstract As gene therapy begins to produce its first clinical successes, interest in ocular gene transfer has grown owing to the favorable safety and efficacy characteristics of the eye as a target organ for drug delivery. Important advances also include the availability of viral and non-viral vectors that are able to efficiently transduce various ocular cell types, the use of intraocular delivery routes and the development of transcriptional regulatory elements that allow sustained levels of gene transfer in small and large animal models after a single administration. Here, we review recent progress in the field of ocular gene therapy. The first experiments in humans with severe inherited forms of blindness seem to confirm the good safety and efficacy profiles observed in animal models and suggest that gene transfer has the potential to become a valuable therapeutic strategy for otherwise untreatable blinding diseases. Abstract | Full Text | PDF (655 kb) |
| Pulsed Laser Microbeam-Induced Cell Lysis: Time-Resolved Imaging and Analysis of Hydrodynamic Effects Biophysical Journal, Volume 91, Issue 1, 1 July 2006, Pages 317-329 Kaustubh R. Rau, Pedro A. Quinto-Su, Amy N. Hellman and Vasan Venugopalan Abstract Time-resolved imaging was used to examine the use of pulsed laser microbeam irradiation to produce cell lysis. Lysis was accomplished through the delivery of 6ns, =532nm laser pulses via a 40×, 0.8 NA objective to a location 10m above confluent monolayers of PtK cells. The process dynamics were examined at cell surface densities of 600 and 1000cells/mm and pulse energies corresponding to 0.7×, 1×, 2×, and 3× the threshold for plasma formation. The cell lysis process was imaged at times of 0.5ns to 50s after laser pulse delivery and revealed the processes of plasma formation, pressure wave propagation, and cavitation bubble dynamics. Cavitation bubble expansion was the primary agent of cell lysis with the zone of lysed cells fully established within 600ns of laser pulse delivery. The spatial extent of cell lysis increased with pulse energy but decreased with cell surface density. Hydrodynamic analysis indicated that cells subject to transient shear stresses in excess of a critical value were lysed while cells exposed to lower shear stresses remained adherent and viable. This critical shear stress is independent of laser pulse energy and varied from ∼60–85kPa for cell monolayers cultured at a density of 600cells/mm to ∼180–220kPa for a surface density of 1000cells/mm. The implications for single cell lysis and microsurgery are discussed. Abstract | Full Text | PDF (360 kb) |
Copyright © 1972 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 12, Issue 6, 666-682, 1 June 1972
doi:10.1016/S0006-3495(72)86111-3
Articles
M.H. Friedman
The description of corneal mechanics and transport developed in part I and used there to describe normal corneal behavior is here applied to corneas whose properties or boundary conditions are abnormal. The predicted effects of changing intraocular pressure, aqueous concentration, and tear tonicity are examined, and these compare favorably with available experimental data. The periodic variation in tear tonicity which accompanies the sleep-wake cycle prevents the cornea from achieving a true steady state, but a time-average steady state, about which corneal behavior oscillates, can be defined. The in vivo effects of endothelial dystrophy and epithelial removal are explained, and it is suggested that the epithelial sodium pump may act homeostatically to maintain corneal thickness in the face of ambient temperature variations. Part II concludes with a discussion, from the standpoint of the present theory, of the role of metabolically coupled water transport in the maintenance of the normal corneal thickness.