Stable Gastric Pentadecapeptide BPC 157 in Rats with Episcleral Veins Cauterization, Glaucoma Model, Preserved Retinal and Optic Nerve Integrity

Abstract

IntroductionWe documented that stable gastric pentadecapeptide BPC 157 in rats with episcleral veins cauterization, glaucoma model, preserved retinal and optic nerve integrity. BPC 157 (LD1 not achieved) was implemented as an anti‐ulcer peptide in IBD trials and now in a multiple sclerosis trial (Curr Pharm Des 2018;24(18):1990–2001). Likewise, beneficial effects of BPC 157 on ocular tissues (Eur J Pharmacol 2016; 771: 211–9; Exp Eye Res 2015;136:9–15; Coll Antropol. 2005;29:321–5) are an especial argument. BPC 157 maintained corneal transparency, total debridement of corneal epithelium cured with no corneal neovascularization, perforating corneal incisions in rats successfully closed and no new vessels, providing a particular healing and vascular effect. Previously, in both short and prolonged terms (6 months), BPC 157 counteracts increased intraocular pressure (IOP) in rats underwent episcleral veins cauterization (FASEB J 2016, 30 (1 suppl), 1201.4; 2017, FASEB J 31 (1 suppl), 666.2). Now, rats underwent episcleral veins cauterization instead exhibiting ganglion cell layer and optic nerve thinning/atrophy, showed close to normal ganglion cell layer and optic nerve thickness, given daily, in the period of 24 h, 4 and 6 weeks.MethodsRandomly assigned operated male Wistar rats, 250g, (two dorsal episcleral veins and one temporal episcleral vein isolated from the surrounding tissues; a cautery specifically applied to the selected vein), were further studied. Now, medication (pentadecapeptide BPC 157 (10μg/kg) (Diagen, Slovenia) intraperitoneally) or an equivolume of 0.9%NaCl (5ml/kg) intraperitoneally (controls)) was applied immediately after surgery, and then once time daily. Histopathological retinal and optic nerve samples were obtained after sacrifice at 24h, 4 and 6‐weeks interval.ResultsAt 24h, 4 and 6 weeks after surgery controls exhibited ganglion cell layer (at 24 h 31.43±1.92 mcm; 4 weeks 21.71±3.73 mcm; 6 weeks 20.43±2.93) and optic nerve thinning (at 24h 735±19.5 mcm; 4 weeks 453.14±7.04 mcm; 6 weeks 421.71±5.99 mcm). All BPC 157 rats exhibited only slight or none ganglion cell layer (at 24 h 41±5.15 mcm; 4 weeks 33±0.76 mcm; 6 weeks 31.14±1.11 mcm) or optic nerve thinning (at 24 h 763±10.80 mcm; 4 weeks 731.86±16.05 mcm; 6 weeks 732.86±7.24 mcm). Differences were statistically significant between control and BPC 157 treated animals at an interval of 4 and 6 weeks (p<0,05). So we conclude that microscopy analysis correlates well with ophthalmoscopy findings published in our previous research (i.e., BPC 157 groups diameter of the optic nerve remained close to normal unlike control's atrophy/thinning of the ganglion cell layer and optic nerve) (Figure 1: Rat optic nerve presentation at 6 weeks, HEx20, saline application (right), BPC 157 regimen (left)).ConclusionPentadecapeptide BPC 157 continuously counteracts the effects of episcleral veins cauterization on morphological changes of ganglion cell layer and optic nerve.Support or Funding InformationMinistry of Science, Education and Sports, Republic of Croatia [grant number 108‐1083570‐3635].This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Stable Gastric Pentadecapeptide BPC 157—Possible Novel Therapy of Glaucoma and Other Ocular Conditions

“…It maintained retinal integrity [ 11 ], recovered pupil function [ 11 , 12 ], and recovered retinal ischemia [ 13 ]. Furthermore, it recovered corneal injuries and recovered corneal transparency [ 14 , 15 , 16 , 17 ]. Recovered corneal injuries and recovered corneal transparency were exemplified in rats who underwent complete corneal abrasion [ 14 ], corneal ulceration [ 15 ], lacrimal gland removal dry eye, or corneal insensitivity [ 16 , 17 ].…”

“…Furthermore, it recovered corneal injuries and recovered corneal transparency [ 14 , 15 , 16 , 17 ]. Recovered corneal injuries and recovered corneal transparency were exemplified in rats who underwent complete corneal abrasion [ 14 ], corneal ulceration [ 15 ], lacrimal gland removal dry eye, or corneal insensitivity [ 16 , 17 ]. In general, the BPC 157 therapy highlights its particular capabilities, cytoprotection [ 7 ] (i.e., translation of the original protection of stomach epithelial cells to the protection of other organs (organoprotection)) and consequent particular vascular effect [ 1 ], wound healing [ 8 ], and neuroprotection [ 9 ].…”

“…Thus, with respect to the known therapy, achievement, and pitfalls [ 31 , 32 , 33 , 34 ], the proposed BPC 157 cytoprotective principle [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ] should be viewed. As emphasized, the cytoprotective arguments are recovery of glaucomatous rats [ 11 ], normalized intraocular pressure [ 11 ], maintaining retinal integrity [ 11 ], recovering pupil function [ 11 , 12 ], recovering retinal ischemia [ 13 ], and corneal injuries [ 14 , 15 , 16 , 17 ]. In particular, counteracting corneal drying, counteracting the loss of corneal sensation, counteracting decrease in blink rate, and maintaining tear production [ 16 , 17 ], have equal effectiveness for topical and systemic application.…”

“…As emphasized, the cytoprotective arguments are recovery of glaucomatous rats [ 11 ], normalized intraocular pressure [ 11 ], maintaining retinal integrity [ 11 ], recovering pupil function [ 11 , 12 ], recovering retinal ischemia [ 13 ], and corneal injuries [ 14 , 15 , 16 , 17 ]. In particular, counteracting corneal drying, counteracting the loss of corneal sensation, counteracting decrease in blink rate, and maintaining tear production [ 16 , 17 ], have equal effectiveness for topical and systemic application. Thereby, the proposed BPC 157 cytoprotective principle should be more viable for further eye therapy.…”

“…Thereby, such recovery of the occlusion/occlusion-like syndrome may be relevant [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. This may be of particular relevance for the recovery of glaucoma (episcleral vein cauterization) [ 11 ] (i.e., rapid decrease in the increased intraocular pressure and preserved retinal integrity) [ 11 ], along with the recovery of pupil function [ 12 ], retinal ischemia [ 13 ], and corneal injuries (i.e., those induced by complete corneal abrasion [ 14 ], corneal ulcer [ 15 ], or dry eye [ 16 , 17 ]). As an example of the tightly interconnected lesions that multiorgan failure causes, there may be a wide interconnected therapy effect in the recovery of the occlusion/occlusion-like syndrome [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”