HIV protease inhibitors provide neuroprotection through inhibition of mitochondrial apoptosis in mice.

Neuroprotection can be achieved by preventing apoptotic death of postmitotic cells. Apoptotic death can occur by either a caspase-dependent mechanism, involving cytochrome c, apoptosis protease-activating factor-1 (Apaf-1), and caspase-9, or a caspase-independent mechanism, involving apoptosis-inducing factor (AIF). HIV protease inhibitors (PIs) avert apoptosis in part by preventing mitochondrial outer membrane permeabilization (MOMP), but the precise mechanism by which they work is not known.

Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.

Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule involved in leukocyte recruitment. Leukocytes and, in particular, macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Previously, we showed a role for VAP-1 in ocular inflammation.

In vivo imaging of endothelial injury in choriocapillaris during endotoxin-induced uveitis.

Early detection of ocular inflammation may prevent the occurrence of structural damage or vision loss. Here, we introduce a novel noninvasive technique for molecular imaging and quantitative evaluation of endothelial injury in the choriocapillaris of live animals, which detects disease earlier than currently possible. Using an established model of ocular inflammation, endotoxin-induced uveitis (EIU), we visualized the rolling and adhesive interaction of fluorescent microspheres conjugated to recombinant P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in choriocapillaris using a scanning laser ophthalmoscope (SLO).

Inhibition of vascular adhesion protein-1 suppresses endotoxin-induced uveitis.

Inflammatory leukocyte accumulation is a common feature of major ocular diseases, such as uveitis, diabetic retinopathy, and age-related macular degeneration. Vascular adhesion protein-1 (VAP-1), a cell surface and soluble molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity, is involved in leukocyte recruitment. However, the expression of VAP-1 in the eye and its contribution to ocular inflammation are unknown.

Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis.

Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD) and several other visual disorders, but the underlying mechanisms remain elusive. Recently, increased expression of monocyte chemoattractant protein 1 (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic retinopathy as well as in the brain tissues of patients with neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Here we report that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an experimental model of RD.

Alteration of leukocyte-endothelial cell interaction during aging in retinal microcirculation of hypertensive rats.

Purpose: Hypertension, one of the more common chronic diseases affecting the elderly, has been reported to influence leukocyte-endothelial cell interaction. The leukocyte-mediated inflammatory process contributes to age-related changes in vessels. This study was designed to evaluate age-related changes in leukocyte-endothelial cell interaction in the hypertensive rat retina.

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation.

Aims: To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC).

Methods: Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy.

Characterization of cytokine responses to retinal detachment in rats.

Purpose: Photoreceptor apoptosis is associated with retinal detachment (RD) induced photoreceptor degeneration. Previously, we demonstrated the importance of caspase activation for RD-induced photoreceptor death in a rat model of RD. However, extracellular signals that precede the activation of caspases and photoreceptor degeneration remain unclear.

Thrombin inhibitor reduces leukocyte-endothelial cell interactions and vascular leakage after scatter laser photocoagulation.

Purpose: Macular edema is one of the most serious adverse effects after retinal scatter laser photocoagulation. It has been suggested that the inflammatory reaction after photocoagulation may be involved in the pathogenesis of macular edema. This study was designed to evaluate quantitatively the inhibitory effects of argatroban, a direct thrombin inhibitor, on leukocyte-endothelial cell interactions and vascular permeability after scatter laser photocoagulation.

Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.

Purpose: Recently, intravitreal injection of corticosteroids has been in wide use as a treatment for diabetic macular edema, and the outcomes have been favorable. However, the exact mechanism remains unclear. The hypothesis for the current study was that intravitreal corticosteroids may improve diabetic retinal edema by amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte stasis (leukostasis).

In vivo three-dimensional evaluation of leukocyte behavior in retinal microcirculation of mice.

Purpose: To evaluate new physiologic and three-dimensional methods for monitoring leukocyte behavior in mouse retina.

Methods: Endotoxin-induced uveitis (EIU) was produced in mice by footpad injection of lipopolysaccharide (LPS). Leukocytes were labeled with acridine orange (AO).

Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes.

Leukocytes play important roles in the pathogenesis of diabetic retinopathy. Recently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been reported to exert various effects in addition to their lipid-lowering ability. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on leukocyte-induced diabetic changes in retinas.

Corneal thickness in eyes following pars plana lensectomy for congenital cataracts.

Purpose: To evaluate the corneal thickness following pars plana lensectomy for congenital cataracts.

Methods: The corneal thickness was measured in 24 eyes of 24 patients with congenital cataracts who had undergone pars plana lensectomy at a mean age of 24 +/- 32 (SD) months. The mean age at the time of our evaluation was 15 +/- 3 years.

In vivo evaluation of retinal injury after transient ischemia in hypertensive rats.

A number of studies have suggested that hypertension affects the pathogenesis of inflammatory reactions in various organs. The objective of this study was to evaluate the effects of hypertension on leukocyte-endothelial interactions after transient retinal ischemia. Transient retinal ischemia was induced for 60 minutes in spontaneously hypertensive rats (SHR) and in age-matched normotensive Wistar-Kyoto rats (WKY).

Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation.

Purpose: Recent evidence suggests that platelets play a major role in ischemia-reperfusion injury, not only through thrombus formation but also through participation in inflammatory reactions with leukocytes. This study was designed to investigate the contribution of platelets in leukocyte recruitment to inflamed regions in vivo.

Methods: Thrombocytopenia was produced in male Long-Evans rats by intravenous injection of anti-platelet serum at 4 hours before ischemia-reperfusion.

Pars plana vitrectomy for epiretinal membrane associated with sarcoidosis.

Purpose: To examine retrospectively the visual outcomes in patients undergoing vitrectomy for epiretinal membranes secondary to sarcoid uveitis.

Methods: Eleven consecutive patients (11 eyes) with epiretinal membrane and uveitis associated with sarcoidosis underwent pars plana vitrectomy.

Results: Nine eyes (82%) gained two or more lines of Snellen visual acuity at 1-12 months after surgery.

Argatroban attenuates leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

Background And Purpose: Argatroban, a direct thrombin inhibitor, has been shown to reduce neural injury after transient cerebral ischemia. It has also been reported that this neuroprotective effect results from an anticoagulant function. This study was designed to evaluate quantitatively the inhibitory effects of argatroban on leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

Glaucoma secondary to pars plana lensectomy for congenital cataract.

Background: To identify risk factors related to the onset of secondary glaucoma in eyes that have undergone pars plana lensectomy for congenital cataract.

Methods: We investigated intraocular pressure levels after pars plana lensectomy for congenital cataract in 80 eyes of 44 patients who were followed up for at least 36 months. Mean age at the time of pars plana lensectomy was 11+/-18 months.