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

Abstract

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease.

Keywords: BPC 157; corneal injuries; glaucomatous rats; intraocular pressure; maintained transparency; pupil function; retinal integrity; retinal ischemia; therapy.

Figure 1

Presentation at 6th week of glaucoma in rats, control (a) and BPC 157-treated rats (B) (fundoscopy). Regularly, all control rats presented with strongly generalized irregularity of the diameter of the blood vessels with severe atrophy of the optic disc with deep excavation, and barely visible (extremely faint presentation) choroidal blood vessels (bright fundus background color) at the end of the sixth post-injury week (a). Contrarily, consequent to the evidence that all BPC 157 regimens, both prophylactic regimen and later, curative regimen, strongly reversed the increased intraocular pressure and abrogated mydriasis, there was normal fundus presentation, the presentation of the normal retinal and choroidal blood vessel presentation, and normal optic nerve presentation at the end of the sixth post-operative week (B) [11].

Figure 2

Presentation at 24 h of occlusion of infrarenal caval vein in rats, control (a), and in BPC 157-treated rats (B) (fundoscopy). Control rats presented with optic disc pallor with a very low filling of the arteries, and a huge veins/arteries ratio. Background choroidal circulation appearance suggests disturbance in circulation, respectively, decreased blood flow (a). Contrarily, there was a normal optic disc with the retinal arteries and veins in BPC 157-treated rats. Background choroidal appearance suggests circulation (B) [23].

Figure 3

Persistent mydriasis in the atropine-induced mydriasis in rats after atropine administration (two drops of 1% atropine/eye) at 48 h in the control rats (a) (red circle), full counteraction of mydriasis and normal pupil presentation in BPC 157 treated rats (B) (small red circle). A similar effect was noted with all BPC 157 regimens. Veho Discovery VMS-004 Deluxe USB microscope camera [12].

Figure 4

Presentation at one week after retrobulbar application of L-NAME in rats, control (a), and in BPC 157-treated rats (B) (fundoscopy). All control rats presented with strong generalized irregular diameter blood vessels with severe atrophy of the optic disc, and extremely poor presentation of the choroidal blood vessels at the end of week 1 (a). Contrarily, all BPC 157-treated rats were presented with normal eye backgrounds and normal presentation of the retinal and choroidal blood vessels at the end of week 1 (B) [14].

Figure 5

Corneal perforating injury. Characteristic gross presentation at 72 h post-surgery in controls (a), and BPC 157-treated rats (B); 60× magnification. Regularly, controls presented with edema at the site of ulceration, growth of new vessels, corneal opacity, and poor transparency. The inflammatory process is active (a). Contrarily, BPC 157-treated rats exhibited an absence of edema at the site of ulceration, markedly attenuated new vessels, corneal transparency, and no signs of inflammatory process at day 3 (B) [15].

Figure 6

Characteristic eye presentation in control rats (lowercase letters), and in BPC 157-treated rats (capitals) after entire epithelium removal, at 16 h (a,B), 24 h (c,D), and 48 h (e,F). The defect area was stained green by fluorescein. Characteristic healing acceleration toward the corneal surface completely healed in the BPC 157-treated eye [14].

Figure 7

Characteristic eye presentation in control rats (lowercase letters), and in BPC 157-treated rats (capitals) after lacrimal gland removal, at 150 min (a,B) and 6 weeks (c,D). In controls, staining the cornea with fluorescein dye and examination under blue light shows positive fluorescein test, and epithelial defects at 150 min (a) and 6 weeks (c). Contrarily, in BPC 157-treated rats, staining cornea with fluorescein dye and examination under blue light shows negative fluorescein test, and absence of the epithelial defects at 150 min (B) and 6 weeks (D) [17].

Figure 8

Though having a wide range of structures and targets, glaucoma therapy (red marks), BPC 157 therapy effects are united by their ability to produce marked definitive cytoprotective effects, as seen with evidenced general recovery in glaucomatous rats (blue marks). There was a shared ability to recover glaucomatous rats [11] and rapidly normalize intraocular pressure [11], maintain retinal integrity [11], recover pupil function [11,12], recover retinal ischemia [13], recover corneal injuries, recover corneal transparency, and regain corneal sensitivity [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]. Contrarily, targets of standard intraocular pressure-lowering drugs [30,31,32,33,34] such as reducing the production of aqueous humor (i.e., beta-blockers, alpha 2-agonists, inhibitors of carbonic anhydrase), promoting drainage through the trabecular meshwork (parasympathomimetics), and through uveoscleral route (prostaglandin derivatives), all remained outside of the cytoprotection implementation [30,31,32,33,34] (gray area). A common concern given the potential impact of the standard intraocular pressure lowering agents on the corneal endothelium is observable [74,75]. Beta-blockers [76,77,78], alpha2-adrenoreceptor agonists [79,80,81], carbonic anhydrase inhibitors [82,83,84,85], and prostaglandin analogs [86,87,88,89] were mentioned. In addition, latanoprost caused miosis, with rebound mydriasis at 24 h post-treatment [150]. Timolol has a delayed effect on miosis (from 4 to 8 h post-treatment), as well as in normal eyes [151,152]. Dorzolamide had no effect [153]. Pilocarpine induced 30 min–12 h miosis in normal eyes [154]. Finally, decreased corneal sensitivity and tear formation appeared with many standard anti-glaucoma agents (i.e., latanoprost, timolol, brimonidine, and dorzolamide) [194,195,196,197]. Note, the standard anti-glaucomatous agents on the increased intraocular pressure had delayed onset [155,156,157,158,159,160,161,162], and in some experimental studies, the effect can be absent [163], or even have the opposite effect [164].