scholarly journals Enhanced Transport and Permeation of a Polymeric Nanocarrier across the Retina by Mixing with ATP upon Intravitreal Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 463
Author(s):  
Kiyoon Kwon ◽  
Youngmin Hwang ◽  
Junyoung Jung ◽  
Giyoong Tae

The outer part of the retina pigment epithelium (RPE) in the retina is the main site of neovascularization associated with retinal diseases. However, various obstacles interrupt the delivery of medicines across the RPE, mainly due to the well-developed tight junctions in the RPE. Currently, there is no practical formulation to overcome this issue. In this study, we demonstrated that simple mixing with adenosine tetraphosphate (ATP) has the potential to greatly enhance the transport and permeation of a polymeric nanocarrier across the retina via intravitreal administration. Chitosan-functionalized, pluronic-based nanocarrier (NC), which can deliver various biomolecules efficiently, was used as a polymeric nanocarrier. Mixing with ATP facilitated the diffusion of the nanocarrier in the vitreous humor by reducing the electrostatic interaction between NC and negatively charged glycosaminoglycans (GAGs) in the vitreous humor. Mixing with ATP also allowed the penetration of NC across the whole retina, and it resulted in a great increase (approximately nine times) in the transport of NC across the retina, as well as spreading it throughout the whole retina upon intravitreal administration in a mouse model. This enhanced permeation across the retina was specific to ATP but not to GTP, suggesting the possibility of P2Y receptor-mediated tight junction disruption by ATP.

Author(s):  
B. J. Panessa-Warren ◽  
J. B. Warren ◽  
H. W. Kraner

Our previous studies have demonstrated that abnormally high amounts of calcium (Ca) and zinc (Zn) can be accumulated in human retina-choroid under pathological conditions and that barium (Ba), which was not detected in the eyes of healthy individuals, is deposited in the retina pigment epithelium (RPE), and to a lesser extent in the sensory retina and iris. In an attempt to understand how these cations can be accumulated in the vertebrate eye, a morphological and microanalytical study of the uptake and loss of specific cations (K, Ca,Ba,Zn) was undertaken with incubated Rana catesbiana isolated retina and RPE preparations. Large frogs (650-800 gms) were dark adapted, guillotined and their eyes enucleated in deep ruby light. The eyes were hemisected behind the ora serrata and the anterior portion of the eye removed. The eyecup was bisected along the plane of the optic disc and the two segments of retina peeled away from the RPE and incubated.


2007 ◽  
Vol 143 (3) ◽  
pp. 323-327 ◽  
Author(s):  
Zeng Yanjun ◽  
Li Guangyu ◽  
Fan Bin ◽  
Wang Qing ◽  
Jie Ying ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9618
Author(s):  
Jérémie Canonica ◽  
Min Zhao ◽  
Tatiana Favez ◽  
Emmanuelle Gelizé ◽  
Laurent Jonet ◽  
...  

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.


2019 ◽  
Vol 103 (10) ◽  
pp. 1406-1412 ◽  
Author(s):  
Wei Dai ◽  
Yih-Chung Tham ◽  
Miao-Li Chee ◽  
Shivani Majithia ◽  
Nicholas Y Q Tan ◽  
...  

Background/aimsTo evaluate the distribution and determinants of outer retinal thickness in eyes without retinal diseases, using spectral-domain optical coherence tomography (SD-OCT).MethodsParticipants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians in Singapore. A total of 5333 participants underwent SD-OCT imaging in which a 6×6 mm2 measurement area centred at the fovea. Outer retinal thickness was defined as the distance from the outer plexiform layer to the retinal pigment epithelium layer boundary.Results7444 eyes from 4454 participants were included in final analysis. Of them, mean age was 58.4 years (SD 8.3), and 2294 (51.5%) were women. Women (121.0±8.1 µm) had thinner average outer retinal thickness than men (125.6±8.2 µm) (p<0.001). Malays (121.4±8.7 µm) had thinner average outer retinal thickness than Indians (124.3±8.6 µm) and Chinese (123.7±7.9 µm) (both p<0.001). In multivariable models, thinner average outer retinal thickness was associated with older age (per decade, β=−1.02, p<0.001), hypertension (β=−0.59, p=0.029), diabetes (β=−0.73, p=0.013), chronic kidney disease (β=−1.25, p=0.017), longer axial length (per mm, β=−0.76, p<0.001), flatter corneal curvature (per mm, β=−2.00, p<0.001) and higher signal strength (β=−1.46, p<0.001).ConclusionIn this large sample of Asian population, we provided normative SD-OCT data on outer retinal thickness in eyes without retinal diseases. Women had thinner outer retina than men. For the first time, these findings provide fundamental knowledge on normative profile of outer retinal thickness in Asians.


1986 ◽  
Vol 43 (2) ◽  
pp. 147-151 ◽  
Author(s):  
A. Bruinink ◽  
S. Dawis ◽  
G. Niemeyer ◽  
W. Lichtensteiger

2021 ◽  
Vol 0 ◽  
pp. 0-0
Author(s):  
Soo-Young Kim ◽  
Yang Zhao ◽  
Hong-Lim Kim ◽  
Youngman Oh ◽  
Qingguo Xu

2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.


Awareness of important anatomical landmarks during vitreoretinal surgery contributes to favorable outcomes in the postoperative period. While external anatomical landmarks include pars plana, ora serrata, and vortex veins, long posterior ciliary nerves, vortex vein ampulla, and optic disc constitute the internal anatomical landmarks for vitreoretinal surgery. The forces that prevent the development of retinal detachment by keeping the retina in place are the retina pigment epithelium pump, the interphotoreceptor matrix, the presence of vitreous gel, and intraocular pressure. The main aim of the surgeon should be removing vitreous as much as possible and releasing vitreoretinal tractions which cause retinal detachment and vitreoretinal interface problems.


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