Stanniocalcin-1 Reduced Intraocular Pressure in Two Models of Ocular Hypertension

Roddy, Gavin W.; Chowdhury, Uttio Roy; Monson, Kjersten J.; Fautsch, Michael P.

doi:10.1080/02713683.2021.1899246

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Indeed, there have been at least seven sets of recent studies where mice (mostly C57BL/6J) have been used to induce OHT using DEX either delivered by injection via subconjunctival injection [ 56 , 57 ], periocular injection at the conjunctival fornix [ 20 ], topical ocular [ 24 , 58 , 59 , 60 ] or via mini-osmotic pumps [ 61 , 62 , 63 ] routes of administration. Additionally, a variety of classes of pharmacological agents and plant-derived extracts have shown IOP-lowering efficacy in the mouse models of steroid-induced OHT, thereby lending further credibility to this particular model ( Table 2 ).…”

Section: Introductionmentioning

confidence: 99%

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

Sharif,

Millar,

Zode

et al. 2024

IJMS

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We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

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Section: Introductionmentioning

confidence: 99%

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

Sharif,

Millar,

Zode

et al. 2024

IJMS

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“…STC-1 was one of the most consistently upregulated molecules following LFA treatment, and later studies revealed that unlike wild-type controls, STC-1 knockout mice were unresponsive to IOP reduction when treated with LFA. Furthermore, topical application of recombinant STC-1 protein lowered IOP in normotensive [ 38 , 39 ] and ocular hypertensive [ 40 ] mice. Finally, topically administered STC-1 showed equivalent IOP reduction as topically administered LFA, but STC-1 did not require the FP receptor for IOP reduction [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility

et al. 2022

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Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though topical therapeutics are typically first line, less than 50% of patients take drops as prescribed. Sustained release technologies that decrease IOP for extended periods of time are being examined for clinical use. We recently identified Stanniocalcin-1, a naturally occurring hormone, as an IOP-lowering agent. Here, we show that a single injection into the anterior chamber of mice with an adeno-associated viral vector containing the transgene of stanniocalcin-1 results in diffuse and sustained expression of the protein and produces IOP reduction for up to 6 months. As the treatment effect begins to wane, IOP-lowering can be rescued with a repeat injection. Aqueous humor dynamic studies revealed an increase in outflow facility as the mechanism of action. This first-in-class therapeutic approach has the potential to improve care and reduce the rates of vision loss in the 80 million people worldwide currently affected by glaucoma.

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“…Ocular hypertension (OHT) is an increase in ocular pressure that occurs during the adolescent years (& GT; 30mm Hg), with open atrial Angle and normal structure and function of optic disc [1]. In this age group, iOP often fluctuates and rises, while high IOP is often the main risk factor for optic nerve damage in glaucoma [2]. The pathogenesis of glaucoma is still unknown, and there is no clear clinical treatment plan.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture at Jingming and Guangming Points Mainly Treats Adolescents with Ocular Hypertension

2022

JCMP

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Ocular hypertension is a disease characterized by continuous increase of intraocular pressure, open angle of chamber, no visual field defect, and normal optic nerve fibers and papilla. Teenagers are in the stage of physical and mental development, and the pressure is characterized by instability, which is characterized by high values measured by applanation tonometer for many times in a period of time, which is called "adolescent ocular hypertension". The pathogenesis of glaucoma is still unclear, and there is no clear treatment plan in clinic. At present, topical symptomatic treatment is mostly used to delay or prevent the onset of glaucoma, but the curative effect is a little poor and the side effects are obvious. In this case, acupuncture is used to treat adolescent ocular hypertension, which is mainly based on near-eyes and far-eyes, supplemented by relevant acupoints, and the effect is good.

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Stanniocalcin-1 Reduced Intraocular Pressure in Two Models of Ocular Hypertension

Cited by 5 publications

References 29 publications

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists

Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility

Acupuncture at Jingming and Guangming Points Mainly Treats Adolescents with Ocular Hypertension

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