latanoprost and Diabetic-Retinopathy

In recent years, with the aging of the population and the frequent use of electronic devices, many eye diseases have shown a linear upward trend, such as dry eye disease, glaucoma, cataract, age-related macular degeneration, and diabetic retinopathy. These diseases are often chronic and difficult to cure. Based on the structure and barrier of the human eye, this review describes the pathogenesis and treatments of several intractable eye diseases and summarizes the advanced ocular drug delivery systems to provide new treatment ideas for these diseases. Finally, we also look forward to the prospect of RNAi therapy in the treatment of eye diseases.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Cataract; Diabetic Retinopathy; Drug Delivery Systems; Dry Eye Syndromes; Eye Diseases; Glaucoma; Humans; Latanoprost; Macular Degeneration; Photosensitizing Agents; Timolol; Treatment Outcome; Verteporfin

Diabetic retinopathy is characterised by morphological lesions secondary to retinal vascular impairment, and it is assumed that changes in the diameter regulation of retinal arterioles are involved in the disease pathogenesis. It has previously been shown that prostaglandin F2α can constrict retinal arterioles in vitro. In the present study, we investigated whether a similar effect could be achieved by topical administration in diabetic patients with dilated retinal arterioles and retinopathy.. Twenty-two type 1 diabetic patients with mild retinopathy and twenty-four matched normal controls were randomized to topical treatment with the prostaglandin F2α agonist latanoprost twice daily for 1 week, followed by similar treatment with the cyclo-oxygenase inhibitor diclofenac, or to receive the two medications in the reverse order. The Dynamic Vessel Analyzer was used to assess the effect of the interventions on the resting diameter of retinal vessels and on the diameter response of retinal arterioles to increased blood pressure (BP) induced by isometric exercise and flicker stimulation.. Latanoprost reduced the resting diameter of retinal arterioles significantly in patients with diabetes (p = 0.01), but had no effect on normal persons. Diclofenac had no effect on the resting diameter of arterioles in either of the groups. The diameter responses to increased BP and flicker stimulation were not significantly changed by any of the treatments.. Long-term prospective studies are needed to study the effect of topical treatment with latanoprost on the consequences of retinal hyperperfusion in retinal vascular diseases such as diabetic retinopathy.

Topics: Administration, Topical; Adult; Antihypertensive Agents; Arterioles; Blood Glucose; Blood Pressure; Cross-Over Studies; Cyclooxygenase Inhibitors; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Diclofenac; Double-Blind Method; Female; Hemostasis; Humans; Intraocular Pressure; Latanoprost; Male; Prostaglandins F, Synthetic; Retinal Artery; Vasodilation; Visual Acuity

The purpose of this study was to investigate whether latanoprost, a prostaglandin F2alpha analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 microM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2+/-15.3 and 23.6+/-9.0 TUNEL positive cells per 0.5 cm(2), respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0+/-3.1 and 11.3+/-3.1 cells per 0.5 cm(2) for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.

Topics: Animals; Apoptosis; Caspase Inhibitors; Cell Line; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dose-Response Relationship, Drug; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Latanoprost; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neuroglia; Neuroprotective Agents; Ophthalmic Solutions; Prostaglandins F, Synthetic; Rats; Rats, Sprague-Dawley; Retina; Retinal Ganglion Cells; Stem Cells