Several adult stem cell types have been found in different parts of the eye, including the corneal epithelium, conjunctiva, and retina. In addition to these, there have been accumulating evidence that some stem‐like cells reside in the transition area between the peripheral corneal endothelium (CE) and the anterior nonfiltering portion of the trabecular meshwork (TM), which is known as the Schwalbe′s Ring region. These stem/progenitor cells may supply new cells for the CE and TM. In fact, the CE and TM share certain similarities in terms of their embryonic origin and proliferative capacity in vivo. In this paper, we discuss the putative stem cell source which has the potential for replacement of lost and nonfunctional cells in CE diseases and glaucoma. The future development of personalized stem cell therapies for the CE and TM may reduce the requirement of corneal grafts and surgical treatments in glaucoma.
Topical and systemic administration of drugs to the eye is highly inefficient and there is a need for controlled, sustained release, particularly for conditions that affect the posterior segment. Various nonimplantable and implantable drug delivery devices have been developed. Colloidal carriers may allow targeted drug delivery and afford protection to substances that are sensitive to degradation, particularly RNA/DNA-based treatments. Gene therapy and cell transplantation are also starting to emerge as alternatives to conventional pharmacological treatment. There is the potential to use existing ocular devices to deliver drugs. In order to exploit this opportunity, modifications to drugs and devices, along with clarification of the appropriate drug dose, must be undertaken. This review will describe some of the treatment options for ocular disease and barriers to drug delivery, discuss the design of existing drug delivery systems and highlight some of the research into combining drug delivery with existing ocular medical devices.
11 February 2011 in British Journal of Ophthalmology
Background Retinal pigment epithelial (RPE) transplantation presents a potential treatment for age-related macular degeneration (AMD). A suitable transplant membrane that can support an intact functioning RPE monolayer is required. Expanded polytetrafluoroethylene (ePTFE) possesses the physical properties required for a transplanting device; however, cells do not attach and spread on ePTFE. This study investigated the ability of surface-modified ePTFE to optimise the growth and function of healthy RPE monolayers. Methods ePTFE discs were modified by ammonia gas plasma treatment. ARPE-19 cells were seeded on the membranes and maintained in media supplemented with retinoic acid and reduced serum. Cell number, morphology and proliferation were analysed. RPE monolayer function was investigated through formation of cell–cell junctions and phagocytosis of photoreceptor outer segments (POS). Results Ammonia gas plasma treatment resulted in enhanced cell growth and good monolayer formation with evidence of cell–cell junctional proteins. Furthermore, RPE monolayers were able to phagocytose POS in a time-dependent manner. Conclusions ePTFE can be surface-modified to support an intact functional monolayer of healthy RPE cells with normal morphology and the ability to perform RPE-specific functions. Following further investigation ePTFE may be considered for use in transplantation.
28 June 2019 in The Journal of Physical Chemistry B
This work represents a detailed investigation into the phase and morphological behavior of synergistic dual-stimuli responsive behavior of poly(N-isopropylacrylamide) nanogels, a material that is of considerable interest as the matrix for in situ forming implants. Nanogels were synthesized in with four different diameters (65, 160, 310 and 450 nm) as monodisperse particles. These different samples were then prepared and characterized as both dilute (0.1 wt %) and concentrated dispersions (2-22 wt %). In dilute form, all the nanogels had the same response to the triggers of physiological temperature and ionic strength. In water, the nanogels would deswell when heated above 32°C, while they would aggregate if heated above this temperature at physiological ionic strength. In concentrated form, the nanogels exhibited a rich range of morphological changes, with liquid, swollen gel, shrunken gel and aggregate structures all possible. The occurrence of these structures was dependent on many factors such as the temperature, ionic strength of solvent, size and zeta potential of nanogel and dispersion concentration. We explored these factors in detail with techniques such as visual studies, rheology, effective volume fraction and shape factor measurement. The different sized nanogels displayed differing phase and morphological behavior, but generally higher concentrations of the nanogels (>7 wt %) yielded gels in water with the transitions dependent on temperature. The smallest nanogel (65 nm diameter) exhibited the most unique behavior; it did not form swollen gel at any concentration tested. Shape factor measurement for the nanogel samples showed that two of the larger three samples (160 and 310 nm) had core-shell structures with denser core crosslinking, while the smallest nanogel sample displayed a homogeneous crosslinked structure. We hypothesize that the smallest nanogels are able to undergo more extensive interpenetration compared to the larger nanogels, which meant that the smallest nanogel was not able to form a swollen gel. In the presence of salt at 12 wt % all the nanogels formed aggregates when heated above 35 °C due to the screening of the electrostatic stabilization by the salt. This work reveals unique behavior of the smallest nanogel with a homogeneous crosslinked structure, its phase and morphological behavior was unlike a particle dispersion, rather it was more similar to a branched polymer solution. In totality, these findings can be used to inform the design of poly(N-isopropylacrylamide) nanogel dispersions for different applications where highly specific spatiotemporal control of morphology is required, for example in the formation of in situ forming implants or pore blocking behavior.
28 September 2012 in Journal of Clinical Periodontology