uf-021 and Retinitis-Pigmentosa

Optic nerve and retinal diseases such as glaucoma, age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are significant public health concerns and have a momentous impact on patients' functional status and quality of life. These diseases are among the most common causes of visual impairment worldwide and account for billions of dollars in healthcare expenditures and lost productivity. The importance of adequate treatment of these conditions and the need for efficacious therapeutic drugs cannot be overstated. Unoprostone continues to be developed as a potential treatment for these debilitating diseases.. This review provides background information on unoprostone isopropyl (unoprostone), a prostanoid and synthetic docosanoid approved for the treatment of open-angle glaucoma and ocular hypertension, and recapitulates safety and efficacy data as it relates to this indication. Additionally, this review describes potential new uses of unoprostone as therapy for dry AMD and RP. A literature search of peer-reviewed publications was performed utilizing PubMed. Searches were last updated on 10 September 2012.. Current data indicate that unoprostone does significantly lower intraocular pressure (IOP) and has a favorable safety and tolerability profile. However, the IOP-lowering effects of unoprostone do not compare with other commercially available prostanoids and it has the disadvantage of a twice-daily rather than once-daily dosing regimen. Nonetheless, recent data suggest that unoprostone may improve neuronal survival and increase ocular blood flow, indicating that it may have some value as a therapy for glaucoma, RP and dry AMD. Further studies are needed to confirm whether unoprostone provides any clinically significant advantage over the other commercially available prostanoids.

Topics: Antihypertensive Agents; Dinoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Macular Degeneration; Ocular Hypertension; Retinitis Pigmentosa; Treatment Outcome

To evaluate the therapeutic effect of topical unoprostone isopropyl (unoprostone) on patients with retinitis pigmentosa (RP).. Forty patients with typical forms of RP were included in the study.Seventeen of 40 patients were treated with 0.12% topical unoprostone twice daily in a randomly selected eye. Patients underwent follow-up examinations every 3 months after treatment. The efficacy of the treatment was monitored by visual acuity and visual field measurement testing using the Humphrey Field Analyzer (HFA: the central 10-2 programme). Moreover, 12 RP patients who were included this study and 12 normal subjects were evaluated in terms of their macular blood flow of both eyes after instillation of unoprostone using the laser speckle method.. One year after treatment, the 'macular sensitivity', calculated by HFA as the average sensitivity of the central 12 points, was preserved in the fellow eyes as well as the unoprostone-treated eyes. On the other hand, that in the eyes of the control RP patient was significantly decreased. Moreover, there were significantly greater improvements of the 'macular sensitivity' in the unoprostone-treated eyes than the fellow eyes. The change ratios of macular blood flow obtained from both RP patients and normal subjects were significantly increased in both the treated and the fellow eyes. No severe side-effects were observed.. These results demonstrate that topical unoprostone might have a therapeutic efficacy in patients with RP as a consequence of the macular bloodflow improvement as well as its direct neuroprotective effect.

Topics: Administration, Topical; Antihypertensive Agents; Dinoprost; Electroretinography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ophthalmic Solutions; Ophthalmoscopy; Prospective Studies; Retinitis Pigmentosa; Treatment Outcome; Visual Acuity

Isopropyl unoprostone (IU), a maxi-K channel activator, is used topically to treat glaucoma, and has been reported to have neuroprotective effects on retinal neurons in vitro and in vivo. The purpose of this non-comparative pilot study was to determine whether topical IU will alter the sensitivity of the central retina in patients with retinitis pigmentosa (RP).. Non-comparative pilot study.. IU was given topically twice a day for 6 months to both eyes of 30 patients with typical RP. The visual acuity was measured with a Japanese Snellen chart, and the mean retinal sensitivities were obtained by fundus-related microperimetry (MP-1). The mean deviation (MD) of the visual field was determined with a Humphrey field analyzer (HFA). All measurements were made before and 6 months after the treatment.. Wilcoxon and the Mann-Whitney U tests (SPSS, SPSS Inc., Chicago, IL).. After the treatment, the mean retinal sensitivity within the central 2° and 10° improved significantly from 12.3 ± 4.8 dB to 14.7 ± 5.5 dB (P = 0.001) and from 9.1 ± 5.4 dB to 11.0 ± 6.2 dB (P = 0.001), respectively.. These short-term results suggest topical IU can improve the central retinal sensitivity in RP patients. It will be necessary to examine longer treatment periods in a controlled study to determine the effectiveness of topical IU in RP patients.

Topics: Adult; Aged; Antihypertensive Agents; Dinoprost; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Recovery of Function; Retina; Retinitis Pigmentosa; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Visual Fields; Young Adult

It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO-loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO-loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO-loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase-3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730-1737, 2016.

Topics: Animals; Dinoprost; Gene Expression Regulation; Mutation; Rats; Rats, Mutant Strains; Retina; Retinitis Pigmentosa; Sensory Rhodopsins

Topics: Administration, Topical; Adult; Ciliary Body; Corneal Edema; Dinoprost; Female; Glaucoma; Humans; Intraocular Pressure; Laser Therapy; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Retinitis Pigmentosa