Immunology and Pathology in Ocular Drug Development

2021 ◽  
pp. 019262332097839
Author(s):  
Meg Ferrell Ramos ◽  
Jacqueline Brassard ◽  
Sharmila Masli
Keyword(s):  
Foreign Protein ◽  
Clear Vision ◽  
Antiangiogenic Factors ◽  
Intraocular Drug Delivery ◽  
Delayed Rejection ◽  
Destructive Inflammation ◽  
Allogenic Tissue ◽  
Tissue Grafts ◽  
Immunosuppressive Cells

Clear vision is dependent on features that protect the anatomical integrity of the eye (cornea and sclera) and those that contribute to internal ocular homeostasis by conferring hemangiogenic (avascular tissues and antiangiogenic factors), lymphangiogenic (lack of draining lymphatics), and immunologic (tight junctions that form blood–ocular barriers, immunosuppressive cells, and modulators) privileges. The later examples are necessary components that enable the eye to maintain an immunosuppressive environment that responds to foreign invaders in a deviated manner, minimizing destructive inflammation that would impair vision. These conditions allowed for the observations made by Medawar, in 1948, of delayed rejection of allogenic tissue grafts in the anterior chamber of mouse eye and permit the sequestration of foreign invaders (eg, Toxoplasma gondii) within the retina of healthy individuals. Yet successful development of intraocular drugs (biologics and delivery devices) has been stymied by adverse ocular pathology, much of which is driven by immune pathways. The eye can be intolerant of foreign protein irrespective of delivery route, and endogenous ocular cells have remarkable plasticity when recruited to preserve visual function. This article provides a review of current understanding of ocular immunology and the potential role of immune mechanisms in pathology observed with intraocular drug delivery.

The Role of the Marketplace in the Post-Covid-19 City of Tomorrow

BUILDER ◽  
2021 ◽  
Vol 289 (8) ◽  
pp. 56-63
Author(s):  
Bartłomiej Buława
Keyword(s):  
Urban Environment ◽  
Development Strategy ◽  
Small Towns ◽  
The Other ◽  
Social Expectations ◽  
Unique Character ◽  
Clear Vision ◽  
Distinct Character ◽  
Effective Development

The role of the marketplace in a city changes from decade to decade. They lose their significance or followings clients’ demands they expand their range of services, creating a unique character and brand. These are places of culture-creating potential, not only of fulfilling basic shopping needs. Six marketplaces of distinct character and impact on the community have been analyzed in order to present their development potential as well as occurring problems. The challenge for many marketplaces, especially smaller ones and those in small towns is the effective development strategy, taking into account current social expectations and consumer trends. When left without a clear vision of the future they often succumb to the competition. On the other hand, when properly developed and transformed they influence the identity of a district or city increasing its multi-functionality. Marketplaces may play a significant role in social integration processes and revitalization of the urban environment in the post-Covid-19 city of tomorrow.

scholarly journals Nanospheres Delivering the EGFR TKI AG1478 Promote Optic Nerve Regeneration: The Role of Size for Intraocular Drug Delivery

ACS Nano ◽  
2011 ◽  
Vol 5 (6) ◽  
pp. 4392-4400 ◽  
Author(s):  
Rebecca Robinson ◽  
Stephen R. Viviano ◽  
Jason M. Criscione ◽  
Cicely A. Williams ◽  
Lin Jun ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optic Nerve ◽  
Nerve Regeneration ◽  
Optic Nerve Regeneration ◽  
Intraocular Drug Delivery ◽  
Egfr Tki

scholarly journals Regulation of sFlt-1 and VEGF secretion by adenosine under hypoxic conditions in rat placental villous explants

2010 ◽  
Vol 299 (6) ◽  
pp. R1629-R1633 ◽  
Author(s):  
Eric M. George ◽  
Kathy Cockrell ◽  
Thomas H. Adair ◽  
Joey P. Granger
Keyword(s):  
Vascular Tissue ◽  
Placental Tissue ◽  
Vegf Receptor ◽  
Extracellular Adenosine ◽  
Adenosine Receptor Antagonist ◽  
Hypoxic Conditions ◽  
Important Regulator ◽  
Antiangiogenic Factors ◽  
Placental Ischemia

The role of adenosine in the regulation of cardiovascular function has long been acknowledged, but only recently has its importance in angiogenesis been appreciated, most notably, through its direct regulation of the proangiogenic growth factor, VEGF. Recent work has established that proangiogenic and antiangiogenic factors, specifically VEGF and and the soluble VEGF receptor fms-like tyrosine kinase-1 (sFlt-1), are directly influenced by hypoxia in placental ischemia. While adenosine has been reported to be an important regulator of VEGF in vascular tissue, the importance of adenosine in regulating VEGF and sFlt-1 in placental tissue is unclear. Here, we have investigated the role of adenosine in the secretion of VEGF and the antiangiogenic protein sFlt-1 in placental villous explants. Under normoxic conditions (6% oxygen), the nonspecific adenosine receptor antagonist, 8-sulphophenyltheophylline (8-SPT) had no effect on either VEGF ( P = 0.38) or sFlt-1 ( P = 0.56) secretion. However, under hypoxic conditions (1% oxygen), 8-SPT attenuated the increase in the secretion of both VEGF and sFlt-1 ( P < 0.05 and P < 0.005, respectively). Exogenous and the adenosine transporter inhibitor dipyridamole (which increases extracellular levels of adenosine) showed differential effects under normoxic conditions: sFlt-1 levels in media increased significantly ( P < 0.05), whereas VEGF was unaffected ( P = 0.67 and P = 0.19, respectively). These data indicate that extracellular adenosine can regulate VEGF and sFlt-1 secretion in the hypoxic placenta and could, therefore, control the balance of these competing angiogenic factors in diseases characterized by placental ischemia.

Influence of hormone environment and donor age on cryopreserved common wombat (Vombatus ursinus) ovarian tissue xenografted into nude mice

2004 ◽  
Vol 16 (7) ◽  
pp. 699 ◽  
Author(s):  
M. Cleary ◽  
J. M. Shaw ◽  
G. Jenkin ◽  
A. O. Trounson
Keyword(s):  
Nude Mice ◽  
Ovarian Tissue ◽  
Follicle Development ◽  
Kidney Capsule ◽  
Oocyte Collection ◽  
Common Wombat ◽  
Tissue Grafts ◽  
Gonadal Status

Developmentally competent oocytes can be collected from xenografted ovarian tissues; however, optimal xenograft conditions need to be established for this technique to be of use in assisted reproduction. In the present study, common wombat ovarian tissue was xenografted under the kidney capsule of nude mice to clarify the role of recipient gonadal status and donor tissue age on graft establishment, follicle development and oocyte recovery. Eighty-nine per cent of all grafts were recovered; of these, 78% contained growing follicles. In female graft recipients, follicle development to the antral stage occurred earlier in ovariectomised recipients compared with intact graft recipients. Similarly, follicle development occurred earlier in recipients of pouch young ovarian tissue grafts when compared with subadult xenografts. Follicle development proceeded to the antral stage in subadult grafts placed under the kidney capsule of male recipient mice, albeit at a slower rate than subadult grafts placed in female recipients. Oocytes were collected from grafts placed in female and male recipients, but no mature oocytes were observed at the time of collection, nor could these oocytes be matured in vitro. The present study demonstrated that common wombat pouch young tissue xenografted to female recipient mice, and subadult ovarian tissue xenografted to male recipient mice, can develop to the antral stage and can therefore facilitate oocyte collection. However, mature oocytes were not obtained using the current protocol.

scholarly journals Evidence against a pivotal role of preformed antibodies in delayed rejection of a guinea pig–to–rat heart xenograft

2000 ◽  
Vol 119 (3) ◽  
pp. 477-487 ◽  
Author(s):  
Helmut Grimm ◽  
Petra Mages ◽  
Gertraut Lindemann ◽  
Mechthild Potthoff ◽  
Ulrich Bohnet ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Rat Heart ◽  
Pivotal Role ◽  
Delayed Rejection

The Effects on Angiogenesis of Relevant Inorganic Chemotherapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Tiziano Marzo ◽  
Diego La Mendola
Keyword(s):  
Metal Ions ◽  
Anticancer Agents ◽  
Review Article ◽  
Pharmacological Effects ◽  
Complex Interactions ◽  
Pathological Conditions ◽  
Copper Zinc ◽  
Antiangiogenic Factors ◽  
The Impact

: Angiogenesis is a key process allowing the formation of blood vessels. It is crucial for all the tissue and organs, ensuring their function and growth. Angiogenesis is finely controlled by several mechanisms involving complex interactions between pro- or antiangiogenic factors and an imbalance in this control chain may result in pathological conditions. Metals as copper, zinc and iron cover an essential role in regulating angiogenesis, thus therapies having physiological metals as target have been proposed. Also, some complexes of heavier metal ions (e.g Pt, Au, Ru) are currently used as established or experimental anticancer agents targeting genomic or non-genomic targets. These molecules may affect the angiogenic mechanisms determining different effects that have been only poorly and non-systematically investigated so far. Accordingly, in this review article we aim to recapitulate the impact on the angiogenic process of some reference anticancer drugs, and how it is connected to the overall pharmacological effects. Also, we highlight how the activity of these drugs can be related to the role of biological essential metal ions. Overall, this may allow a deeper description and understanding of the antineoplastic activity of both approved or experimental metal complexes, providing important insights for the synthesis of new inorganic drugs able to overcome resistance and recurrence phenomena.

scholarly journals The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2296
Author(s):  
Maurice Michel ◽  
Leonard Kaps ◽  
Annett Maderer ◽  
Peter R. Galle ◽  
Markus Moehler
Keyword(s):  
Colorectal Cancer ◽  
Stromal Cells ◽  
Tp53 Gene ◽  
Cancer Associated Fibroblasts ◽  
P53 Mutations ◽  
The One ◽  
Immunosuppressive Cells ◽  
And Personalized Medicine ◽  
Therapy Treatment

Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.

scholarly journals Asymmetric Membranes: A Potential Scaffold for Wound Healing Applications

Symmetry ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1100 ◽  
Author(s):  
Seyyed Mojtaba Mousavi ◽  
Maryam Zarei ◽  
Seyyed Alireza Hashemi ◽  
Seeram Ramakrishna ◽  
Wei-Hung Chiang ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Production Process ◽  
Healing Process ◽  
Skin Lesions ◽  
Asymmetric Membranes ◽  
Preparation Methods ◽  
Bacterial Penetration ◽  
Tissue Grafts ◽  
Native Skin

Currently, due to uprising concerns about wound infections, healing agents have been regarded as one of the major solutions in the treatment of different skin lesions. The usage of temporary barriers can be an effective way to protect wounds or ulcers from dangerous agents and, using these carriers can not only improve the healing process but also they can minimize the scarring and the pain suffered by the human. To cope with this demand, researchers struggled to develop wound dressing agents that could mimic the structural and properties of native skin with the capability to inhibit bacterial growth. Hence, asymmetric membranes that can impair bacterial penetration and avoid exudate accumulation as well as wound dehydration have been introduced. In general, synthetic implants and tissue grafts are expensive, hard to handle (due to their fragile nature and poor mechanical properties) and their production process is very time consuming, while the asymmetric membranes are affordable and their production process is easier than previous epidermal substitutes. Motivated by this, here we will cover different topics, first, the comprehensive research developments of asymmetric membranes are reviewed and second, general properties and different preparation methods of asymmetric membranes are summarized. In the two last parts, the role of chitosan based-asymmetric membranes and electrospun asymmetric membranes in hastening the healing process are mentioned respectively. The aforementioned membranes are inexpensive and possess high antibacterial and satisfactory mechanical properties. It is concluded that, despite the promising current investigations, much effort is still required to be done in asymmetric membranes.

Sign in / Sign up

Export Citation Format

Share Document