Secondary neuroprotective effects of hypotensive drugs and potential mechanisms of action

Shih, Grace; Calkins, David J.

doi:10.1586/eop.12.13

Cited by 29 publications

(22 citation statements)

References 112 publications

(100 reference statements)

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“…11,[13][14][15][16][17][18] While topical administration of drug is the preferred method of delivery for most ocular diseases, including glaucoma, this route is very inefficient. 7,49 In fact, less than 5% of drug applied topically reaches its target tissue within the eye, which necessitates the frequent dosing (up to 3 times daily) required for most topical ocular drugs. 50,[59][60][61] Many factors, including ocular anatomy, blinking, and tear film, limit the bioavailability of topical ocular drugs.…”

Section: Discussionmentioning

confidence: 99%

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Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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Purpose: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.Methods: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.Results: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P , 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P , 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P , 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.Conclusions: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.Translational Relevance: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

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Section: Discussionmentioning

confidence: 99%

“…6 First line treatment for glaucoma is the use of topical eye drops containing IOP-lowering drugs. 7 While lowering IOP can slow disease progression, it does not necessarily prevent RGC degeneration. 6,8 In fact, glaucomatous progression may continue in as many as 50% of glaucoma patients on a regimen to lower IOP.…”

Section: Introductionmentioning

confidence: 99%

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure

Lambert

Carlson

Ende

et al. 2015

Trans. Vis. Sci. Tech.

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“…The use of IOP-lowering drugs, the current mainstay treatment, is often insufficient to prevent progressive visual loss in glaucoma patients. Recent studies of potential treatments have therefore shifted to assessment of neuroprotective strategies to promote neuronal survivability and thereby preserve function (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

Akopian¹,

Kumar²,

Ramakrishnan³

et al. 2017

Journal of Clinical Investigation

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The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma.

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“…Однак дані стосовно їхнього впливу на ВОТ є обмеженими та суперечливими. Таким чином, в ургентній офтальмології (гострий напад глаукоми, гостра офтальмогіпертензія) препаратами вибору є β-адреноблокатори для зниження ВОТ, які доцільно комбінувати з нейропротекторною терапією [12]. Для оптимізації фармакотерапії синдрому ВОТ нашу увагу привернуло одне із похідних ада мантану -1-адамантилетилокси-3-мор-фо ліно-2-пропанолу гідрохлорид під умов-ною назвою адемол, якому притаман ний нейропротекторний ефект, котрий реалізу-ється за рахунок його модулювального впливу на активність НМДА-рецепторів [13].…”

Section: вступunclassified