Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK

Mohan, Rahul; Hutcheon, Audrey E. K.; Choi, Rosan; Hong, J.; Lee, JongSoo; Mohan, Rajiv R.; Ambrósio, Renato; Zieske, James D.; Wilson, Steven E.

doi:10.1016/s0014-4835(02)00251-8

Cited by 374 publications

(342 citation statements)

References 30 publications

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“…Maltseva et al (2001) based on in vitro studies, suggested that fibroblast growth factor plays an important role in myofibroblast trans-differentiation back to the progenitor cell. However, Mohan et al (2003) noted apoptotic cells that appeared to coincide with myofibroblasts at 1 and 3 months after −9.0 diopter PRK. Similar apoptotic anterior stromal cells were noted in this study in some corneas that had haze, especially after either −4.5 diopter PRK with marked surface irregularity (group III or IV) or −9.0 diopter PRK (group VI).…”

Section: Discussionmentioning

confidence: 97%

“…Mohan et al (2003) noted that the peak in haze tends to occur at approximately 1 month after PRK in rabbits, but also diminishes over the subsequent months. Maltseva et al (2001) based on in vitro studies, suggested that fibroblast growth factor plays an important role in myofibroblast trans-differentiation back to the progenitor cell.…”

Section: Discussionmentioning

confidence: 99%

“…Eight groups were included, as shown in Table 1: (I) −4.5 diopter PRK, (II) −4.5 diopter PRK with a metallic screen mesh inserted in the path of excimer laser ablation ( Fig. 1A and B) for the final 10% of excimer laser pulses, (III) −4.5 diopter PRK with screening of the final 30% of excimer laser pulses, (IV) −4.5 diopter PRK with screening of the final 50% of excimer laser pulses, (V) −4.5 diopter PRK with screening of the final 50% of PRK pulses followed by phototherapeutic keratectomy (PTK)-smoothing, (VI) −9.0 diopter PRK for high myopia (as a positive control for myofibroblast generation and haze, Mohan et al, 2003), (VII) −9.0 diopter PRK followed by PTK-smoothing, and (VIII) unwounded control corneas. In preliminary experiments we noted no difference between metal and plastic screens with openings of the same size.…”

Section: Animals and Surgerymentioning

confidence: 99%

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Stromal haze, myofibroblasts, and surface irregularity after PRK

Netto

Mohan

Sinha

et al. 2006

Experimental Eye Research

245

204

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The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze.Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups:Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr or 4 weeks after surgery and histochemical analysis was performed on corneas for apoptosis (TUNEL assay), myofibroblast marker alpha-smooth muscle actin (SMA), and integrin α4 to delineate the epithelial basement membrane.Slit-lamp grading revealed severe haze formation in corneas in groups IV and VI, with significantly less haze in groups II, III, and VII and insignificant haze compared with the unwounded control in groups I and V. Analysis of SMA staining at 4 weeks after surgery, the approximate peak of haze formation in rabbits, revealed low myofibroblast formation in group I (1.2 ± 0.2 cells/400× field) and group V (1.8 ± 0.4), with significantly more in groups II (3.5 ± 1.8), III (6.8 ± 1.6), VII (7.9 ± 3.8), IV (12.4 ± 4.2) and VI (14.6 ± 5.1). The screened groups were significantly different from each other (p <0.05), with myofibroblast generation increasing with higher surface irregularity in the −4.5 diopter PRK groups. The −9.0 diopter PRK group VI had significantly more myofibroblast generation than the −9.0 diopter PRK with PTK-smoothing group VII (p <0.01). Areas of basement membrane disruption were demonstrated by staining corneas for integrin α4 and were prominent in corneas with grade I or higher haze. SMA-positive myofibroblasts tended to be present sub-adjacent to basement membrane defects. Late apoptosis was detected at 1 month after surgery within clusters of myofibroblasts in the sub-epithelial stroma. In conclusion, these results demonstrated a relationship between the level of corneal haze formation after PRK and the level of stromal surface irregularity. PTK-smoothing with methylcellulose was an effective method to reduce stromal surface irregularity and decreased both haze and associated myofibroblast density. We hypothesize that stromal surface irregularity after PRK for high myopia results in defective basement membrane regeneration and increased epithelium-derived TGFβ signalling to the stroma that increases myofibroblast generation. Late apoptosis appears to have a role in the disappearance of myofibroblasts and haze over time.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Surgerymentioning

confidence: 99%

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Stromal haze, myofibroblasts, and surface irregularity after PRK

Netto

Mohan

Sinha

et al. 2006

Experimental Eye Research

245

204

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“…1), incisional injuries from scalpel blades or microkeratomes, or even significant pressure of a contact lens on the epithelial surface Wilson, 1998;Helena, et al, 1998;Mohan, et al, 2003). Most commonly, apoptosis is detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, and with this assay the labeling peaks at approximately four hours after epithelial injury .…”

Section: Early Phase Apoptosismentioning

confidence: 99%

“…Thus, in studies that included unwounded control corneas in rabbits (Helena, et al, 1998, Mohan, et al, 2003, Szentmary, 2005, mice , or humans (Kim, et al, 1999), almost no apoptotic keratocytes or other stromal cells were noted in control corneas, even when dozens of tissue sections were examined. Apoptotic keratocytes may, however, be noted away from sites of epithelial injury in keratoconus corneas (Kim, et al, 1999), leading to the hypothesis that abnormally high levels of ongoing keratocyte apoptosis could play a role in the pathophysiology of this ectatic corneal disease (Kim, et al, 1999;Chwa, et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in the initiation, modulation and termination of the corneal wound healing response

Wilson

Chaurasia

Medeiros

2007

Experimental Eye Research

137

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Stromal keratocyte apoptosis has been well-characterized as an early initiating event of the corneal wound healing response, triggering subsequent cellular processes that include bone marrow-derived cell infiltration, proliferation and migration of residual keratocyte cells, and, in some circumstances, generation of myofibroblast cells. Recent studies, however, have suggested a more general role for apoptosis in the overall stromal wound healing response that includes modulation and termination functions. This review article highlights, and ties together, recent studies that have demonstrated the important role apoptosis likely plays in the weeks to months following an initial insult to the cornea -depending on the type and extent of corneal injury.

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Histologic, Ultrastructural, and Immunofluorescent Evaluation of Human Laser-Assisted In Situ Keratomileusis Corneal Wounds

Dawson¹

2005

Arch Ophthalmol

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To evaluate human corneas after laserassisted in situ keratomileusis at different postoperative intervals.Methods: Thirty-eight postmortem corneas from 20 patients with postoperative intervals from 2 months to 6.5 years after laser-assisted in situ keratomileusis surgery were collected from eye banks. The corneas were trisected and processed for conventional histologic analysis, transmission electron microscopy, and immunofluorescence.Results: Light microscopy and transmission electron microscopy showed focal undulations in Bowman layer, focal epithelial hypertrophic modifications, and a variably thick (range, 0.4-16.4-µm) lamellar stromal interface scar in all specimens. The flap wound margin, which was adjacent to the epithelium, healed by producing an approximately 8-µm-thick hypercellular fibrotic stromal scar,

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Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK

Cited by 374 publications

References 30 publications

Stromal haze, myofibroblasts, and surface irregularity after PRK

Stromal haze, myofibroblasts, and surface irregularity after PRK

Apoptosis in the initiation, modulation and termination of the corneal wound healing response

Histologic, Ultrastructural, and Immunofluorescent Evaluation of Human Laser-Assisted In Situ Keratomileusis Corneal Wounds

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