A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy

Roberti, Gloria; Tanga, Lucia; Parisi, Vincenzo; Sampalmieri, M.; Centofanti, Marco; Manni, Gianluca

doi:10.4103/0301-4738.133484

Cited by 49 publications

(46 citation statements)

References 13 publications

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“…However, even with these barriers, approximately 1% of agents applied directly to the cornea reach the retina depending on the agent’s vehicle (Ahmed and Patton, 1985; Loftsson and Brewster, 2008), either working its way from the anterior of the eye to the retina, or by drops that are absorbed through the back of the eye as eye drops follow the curvature of the eye structure. Treating the retina directly with neuroprotective eye drops has recently been used to analyze N-methyl-N-nitrosourea-induced photoreceptor cell death (Lin et al, 2014), to study glaucomatous optic neuropathy (Roberti et al, 2014) and to preserve visual function at the retinal ganglion cell layer (Prokai-Tatrai et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Retinal ganglion cell neuroprotection induced by activation of alpha7 nicotinic acetylcholine receptors

Mata

Linn²,

Linn

2015

Neuropharmacology

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The α7nAChR agonist, PNU-282987, has previously been shown to have a neuroprotective effect against loss of retinal ganglion cells (RGCs) in an in vivo glaucoma model when the agent was injected into the vitreous chamber of adult Long Evans rat eyes. Here, we characterized the neuroprotective effect of PNU-282987 at the nerve fiber and retinal ganglion cell layer, determined that neuroprotection occurred when the agonist was applied as eye drops and verified detection of the agonist in the retina, using LC/MS/MS. To induce glaucoma-like conditions in adult Long Evans rats, hypertonic saline was injected into the episcleral veins to induce scar tissue and increase intraocular pressure. Within one month, this procedure produced significant loss of RGCs compared to untreated conditions. RGCs were quantified after immunostaining with an antibody against Thy 1.1 and imaged using a confocal microscope. In dose-response studies, concentrations of PNU-282987 were applied to the animal’s right eye two times each day, while the left eye acted as an internal control. Eye drops of PNU-282987 resulted in neuroprotection against RGC loss in a dose-dependent manner using concentrations between 100 µM and 2 mM PNU-282987. LC/MS/MS results demonstrated that PNU-282987 was detected in the retina when applied as eye drops, relatively small amounts of PNU-282987 were measured in blood plasma and no PNU-282987 was detected in cardiac tissue. These results support the hypothesis that eye drop application of PNU-282987 can prevent loss of RGCs associated with glaucoma, which can lead to neuroprotective treatments for diseases that involve α7nAChRs.

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Section: Discussionmentioning

confidence: 99%

Retinal ganglion cell neuroprotection induced by activation of alpha7 nicotinic acetylcholine receptors

Mata

Linn²,

Linn

2015

Neuropharmacology

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“…Follow-up was 2 years Pfeiffer 2002 Not the population of interest: RCT of latanoprost and timolol; excluded because the included participants had either POAG or ocular hypertension. Trial period was 6 months Roberti 2014 Short-term trial: RCT of topical citicoline plus hypotensive therapy compared with hypotensive therapy alone in people with OAG. Trial period was 3 months Robin 1993 Short-term trial: RCT of 1% topical apraclonidine in reducing IOP following combined cataract surgery in people with POAG.…”

Section: Appendicesmentioning

confidence: 99%

Neuroprotection for treatment of glaucoma in adults

Sena

Lindsley

2017

Cochrane Database of Systematic Reviews

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Background Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. Objectives The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016. Selection criteria We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years. Data collection and analysis Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until study investigators provide additional study details. We documented reasons for excluding studies from the review. Main results We included one multicenter RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was progression of visual field loss after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, the investigators excluded 12 (6.3%) after randomization; 77 participants (40.5%) did not complete four years of follow-up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%). Of those remaining in the study at four years, participants assigned to brimonidine showed less progression of visual field loss than participants assigned to tim...

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“…Until today, there have been no neuroprotectors among eye drops, since their molecules are large and lipophilic, and thus do not readily penetrate the ocular tissues [9,12]. The experimental study [12] has demonstrated that the ophthalmic solution OMK1 based on citicoline 2% in combination with high molecular weight hyaluronic acid and benzalkonium chloride at low concentration, 0.01%, guarantees the passage of the molecule in the posterior segment, reaching the retina and the optic nerve head.…”

Section: Resultsmentioning

confidence: 99%

“…Citicoline has been used as a topically administered neuroprotective drug. There have been very few reports on the use of citicoline in the medical treatment of glaucoma, as a complement to hypotensive therapy [6,9], which resulted in improvements in visual fields and electrophysiologic indices of retinal function, although the effect was short term (approximately 30 days after washing off the medication). We aimed to maximize the therapeutic effect by forming a drug depot in ocular tissues, and to prolong the effect by using a new route (non-topical and non-injection) for delivery.…”

Section: Introductionmentioning

confidence: 99%

On the treatment of degeneration of the macula and posterior pole

Konovalova¹,

Khramenko²,

Guzun³

et al. 2018

Oftalmol Zh

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The field of degeneration of the macula and posterior pole (DMPP) is of outstanding medical and social significance as the disease is of high prevalence and leads to loss of general working capacity. Purpose: To determine the efficacy of conservative treatment with endonasal iontophoresis of Omk2, and the degree of stabilization of visual functions after this treatment in patients with DMPP. Materials and Methods: Thirty-two patients (45 eyes; age, 51 to 75 years) with DMPP were examined and received treatment with endonasal iontophoresis of Omk2. The eye examination included visual acuity, retinal light sensitivity, threshold assessment with macula tester, perimetry and ophthalmoscopy, and was performed before and after treatment. Results: In all patients with DMPP, iontophoresis of Omk2 contributed to apparent improvement in functional activity of the retina, which was achieved due to antioxidative, neurotropic, anti-edema and anti-angiogenetic properties of the drug. In particular, mean uncorrected visual acuity (UCVA) in patients of group 1 improved by 25%, from 0.6 to 0.85, and UCVA in 49% of patients of group 2 improved by 0.01-0.02, which improved the level of social rehabilitation of these patients. In patients with DMPP, the treatment with iontophoresis of Omk2 resulted in improvements in the functional activity of the retinal photopic system and foveal afferent system (as assessed by the Haidinger's brushes test), and retinal blood flow in the posterior pole (as assessed by the blue field technique) by 33-43%, 14%, and 40%, respectively. This demonstrates that the treatment strategy has the beneficial impact on the function of the visual system, and iontophoresis of Omk2 is a pathogenetically reasonable approach to the management of DMPP. Conclusion: Iontophoresis of Omk2 was found to be beneficial for the function of the visual system, and a pathogenetically reasonable approach to the management of DMPP.

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A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy

Cited by 49 publications

References 13 publications

Retinal ganglion cell neuroprotection induced by activation of alpha7 nicotinic acetylcholine receptors

Retinal ganglion cell neuroprotection induced by activation of alpha7 nicotinic acetylcholine receptors

Neuroprotection for treatment of glaucoma in adults

On the treatment of degeneration of the macula and posterior pole

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