Abstract
Retinal laser injuries are often associated with aberrant migration of the retinal pigment epithelium (RPE), which can cause expansion of the scar beyond the confines of the original laser burn. In this study, we devised a novel method of laser-induced injury to the RPE layer in mouse models and began to dissect the mechanisms associated with pathogenesis and progression of laser-induced RPE injury. We have hypothesized that the proto-oncogene receptor, c-Met, is intimately involved with migration of RPE cells, and may be an early responder to injury. Using transgenic mouse models, we show that constitutive activation of c-Met induces more robust RPE migration into the outer retina of laser-injured eyes, while abrogation of the receptor using a cre-lox method reduces these responses. We also demonstrate that retinal laser injury increases expression of both HGF and c-Met, and activation of c-Met after injury is correlated with RPE cell migration. RPE migration may be responsible for clinically significant anatomic changes observed after laser injury. Abrogation of c-Met activity may be a therapeutic target to minimize retinal damage from aberrant RPE cell migration.
Highlights
Lasers have been broadly applied in our world and laser instruments are being increasingly employed in a vast variety of fields, including military, health, educational, and commercial laboratories [1]
We show that constitutive activation of c-Met induces more robust retinal pigment epithelium (RPE) migration while abrogation of the receptor reduces these responses, suggesting that modulation of the c-Met activity may influence post-injury responses to laser burns
No obvious morphological disorganization of retina was found at early stage after the laser burns (Figure 2A and 2D), apoptotic cells were detected in seemingly injured retinas
Summary
Lasers have been broadly applied in our world and laser instruments are being increasingly employed in a vast variety of fields, including military, health, educational, and commercial laboratories [1]. Even in the field of ophthalmology the use of laser has increased many folds. Sections were washed in PBS and subjected to immunohistochemistry using the Vectastain ABC kit with alkaline phosphatase method and resolved with Vector Red (Vector laboratories, Burlingame, CA). 59-TTCCCAGCTGGTCTATGGTC-39 59-TGGTGCTGACTGCATTTCTC-39 59-ATGAAATCCACCCAACCAAA-39 59-TCTGAATTTGAGCGATGCTG-39 59-AACAGCAACTCCCACTCTTC-39 59-CCTCTCTTGCTCAGTGTCCT-39 doi:10.1371/journal.pone.0040771.t002 under an IX51 Olympus inverted fluorescent microscope (Olympus Corporation, Tokyo, Japan) both under visible light and epifluorescence for better detection of the highly fluorescent rhodamine Vector Red pigment. Effect of Laser Injury on Expression of c-Met and HGF in B6 Mice A greyscale fundus image was sandwiched with its corresponding fluorescence image, which was itself assigned an arbitrary color (green, blue or red).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
