Femtosecond dovetail penetrating keratoplasty: surgical technique and case report.

Br J Ophthalmol. 2009 Jul; 93(7): 861-3Lee J, Winokur J, Hallak J, Azar DTAIM: To report a dovetail configuration for femtosecond-enabled penetrating keratoplasty (PK) with the corresponding laser parameters and suturing technique. METHODS: A 40-year-old man, with a history of penetrating corneal injury as a child, underwent femtosecond-enabled dovetail keratoplasty, anterior vitrectomy and secondary intraocular lens suturing to repair his corneal scar and aphakia. A partial thickness dovetail pattern was performed in the recipient cornea using the femotsecond laser. The posterior side-cut was initiated approximately 100 microm anterior to the Descemet membrane and extended obliquely towards the outer edge of a ring lamellar cut, positioned at approximately 300 microm stromal depth. The anterior side-cut was extended from the internal edge of the ring lamellar cut to the corneal surface. Using an artificial chamber, the femtosecond laser was used to create a full-thickness 0.2 mm oversized femtosecond-enabled dovetail trephination with similar anterior lamellar depth (approximately 300 microm). Wound closure, using interrupted 10-0 nylon sutures, was guided by preplaced radial alignment laser microincisions and tongue-in-groove midstromal suture positioning. RESULTS AND DISCUSSION: Excellent alignment and stability of the donor and recipient tissue were observed immediately postoperatively and 5 months after surgery. The feasibility of the "dovetail" pattern of PK and the tongue-in-groove suture positioning is demonstrated.

Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease.

Dis Model Mech. 2009 Jul-Aug; 2(7-8): 344-58Boudoulas KD, Hatzopoulos AKAcute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.

Scarless Fetal Mouse Wound Healing May Initiate Apoptosis Through Caspase 7 and Cleavage of PARP.

J Surg Res. 2009 May 3; Carter R, Sykes V, Lanning DINTRODUCTION: Apoptotic mechanisms are thought to be important in wound healing for the removal of inflammatory cells and evolution of granulation tissue. However, little is understood about the signal, propagation, and mechanisms responsible for triggering cell death in tissue injury, particularly during fetal wound repair. Understanding these signals may lead to insights regarding scarless wound healing. We hypothesized that differences in apoptosis would exist in mid- (E15) compared with late-gestational (E18) mice subjected to cutaneous wounds. We examined early apoptotic signals that may be initiated following tissue injury. METHODS: Pregnant, time-dated mice underwent laparotomy and hysterotomy on embryonic day 15 (E15) and 18 (E18). Full-thickness, excisional cutaneous wounds were made on the dorsum of the fetuses and dorsal skin harvested 15 and 45 min after wounding. Unwounded dorsal skin from additional fetuses collected at the same time points served as controls. The skin was processed to obtain protein, then levels of caspase 3, caspase 7, and poly ADP-ribose polymerase (PARP) were measured by Western blot. Cyclophilin levels were measured to ensure equal loading of protein. Histone-associated DNA complex formation was examined to provide further evidence of cellular apoptosis. RESULTS: There were no differences in total caspase 3 levels between E15 and E18 fetal tissue with or without wounding, nor was any cleavage of caspase 3 noted in any group. However, cleaved caspase 7 was present in the E15 skin with a >2-fold increase following wounding at both 15 and 45 min, yet absent in the E18 groups. Furthermore, levels of cleaved PARP were also increased by >2-fold at both 15 and 45 min in E15 wound groups, whereas a relatively small amount was only seen in the E18 wound groups at 45 min. DNA-histone fragmentation ELISA assay showed a 5-fold increase in the enrichment of histone-associated DNA fragments in the E15 wounded tissue compared with the time-matched controls at 45 min. This was not seen with the E18 tissue. CONCLUSIONS: Previously, we demonstrated that cutaneous wounds in E15 fetal mice heal in a scarless manner, while similar wounds in E18 mice heal with scar formation. Results from our current work demonstrate differences in apoptosis in mid- compared with late-gestational mouse skin as well as shortly after wounding. Our results suggest that in mid-gestational wounds, activation of apoptotic pathways may be mediated through effector caspase 7 signals with inactivation of PARP. This initiation of apoptotic signals following tissue injury may play a role in scarless wound repair.

Pigment Epithelium Derived Factor (PEDF) attenuated capsaicin induced neurotrophic keratouveitis.

Invest Ophthalmol Vis Sci. 2009 Jun 24; Feher J, Kovacs I, Pacella E, Keresz S, Spagnardi N, Balacco-Gabrieli CPurpose: To reveal the influence of retrobulbar capsaicin treatment on rats' eyes and to test protective effects of PEDF, a known neurotrophic and antiangiogenic substance on neurotrophic keratouveitis. Methods: A single retrobulbar injection of capsaicin (50 mg/kg ) was performed in young rats and the effect of 3.2 or 6.4 microg PEDF with retrobulbar administration was recorded. Tear fluid alterations were evaluated with Schirmer test, corneal alterations with slit lamp biomicroscopy. Histopathologic alterations were studied with light and electron microscopy. Number of leukocytes (myeloid cells) in the anterior and posterior chambers, peripheral retina and vitreous were quantitatively evaluated. Results: Reduced tear secretion was found in capsaicin treated rats as compared to control, but this effect was significantly attenuated by PEDF. Corneal ulceration developed and was followed by scar formation and neovascularisation in the capsaicin treated rats and it was also significantly attenuated with PEDF treatment. Leukocyte infiltration of the anterior and posterior chambers, as well as those of the peripheral retina and vitreous was also observed in capsaicin treated eyes, and was significantly reduced by PEDF treatment. Protective effects of PEDF were dose dependent for each parameters even if the treatment was initiated at the day 14 after capsaicin challenge. Conclusions: PEDF accelerated recovery of tear secretion, as well as prevented capsaicin-induced neurotrophic keratouveitis and peripheral vitreoretinal inflammation. These effects of PEDF described here for the first time, may have a clinical application in inflammatory and neovascular diseases of the eye.