Academic Ophthalmology
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Ocular Surface Research

Aim

We aim to prevent ocular surface-blindness, which is can be avoidable but has devastating consequences to the patient and healthcare system, by combating the visually debilitating conditions affecting the ocular surface.

 

 

SEM-Image Cells on Amniotic Membrane

 

Research issues

Trauma, inflammation and infection at the ocular surface causes damage, which without effective treatment, accounts for up to 2 million new cases of monocular blindness every year, adding to the existing 39 million cases worldwide.

This has significant physical and psychological impact on the patient as well as having profound consequences for their families and socio-economic impact on the community.

The high financial cost of avoidable visual loss makes it an important public health concern. Unfortunately, current treatment strategies for these patients are subject to many limitations, therefore creating a great need for research in this area.

What we are doing about...

1. Ocular surface healing

Limbal stem cells

The integrity of the corneal surface epithelium is essential for maintaining clarity of vision. When damaged, the surface is regenerated by the stem/progenitor cells located at the limbus. Damage to limbal stem cells and the corneal surface can lead to visual impairment and blindness/debilitation. Projects in this area focus on characterising and expanding limbal to understand their biology and to exploit them for clinical use.

 

Mesenchymal stem cells

Isolation and expansion of limbal stem cells is challenging. Therefore, identifying a widely available and stable alternative would have huge research and therapeutic potential. Mesenchymal stem cells are an example of such a cell type that has been used for the generation of other tissues.

Academic Ophthalmology discovered mesenchymal stem cells residing in the corneal stoma, therefore redefining the conventional keratocyte. Most importantly we isolated a population of corneal stromal multipotent stem cells that have the ability to produce corneal epithelium, and are investigating their role in vivo corneal regeneration. We are currently developing methodologies to develop these cells as a bankable technology for corneal regeneration and engineering proposes.

 

2. Ocular surface regeneration

Amniotic membrane

Amniotic membrane is waste product of pregnancy, but possesses unique regenerative properties. Amnion has been extensively used for the regeneration of many tissues including the ocular surface where it has become a standard treatment for corneal defects. Unfortunately, amnion use has limitations that are associated with the non-standardised way it is prepared, preserved, and clinically applied.
We have a long-standing amnion research programme and have extensively characterised the composition and functional properties.

Our research has lead to the development, in collaboration with the British Military, of a highly innovative standardised amnion-derived product, known as Omnigen. Our department is working towards commercialising Omnigen for improved patient care. (More information)

 

Corneal mimetic constructs

With 39 million corneal blind worldwide, developing affordable technologies as replacement tissue for corneal regeneration is a leading healthcare and therefore scientific priority. The structure of the cornea and its biochemical and cellular composition is complex; therefore effective recapitulating the architecture is a major engineering challenge. Translating developing technologies to large-scale manufacturing and into a cost effective, affordable and beneficial process, able to address the global need is an even greater challenge.

We, and our multidisciplinary collaborators, have a portfolio of complementary projects to investigate all the aspects of this enormous challenge. These include investigating the range of available synthetic and biological material alternatives to determine the most suitable corneal compatible material; devising the most efficient engineering process to achieve an effective corneal mimetic scaffold with the desired physical, biological and optical properties; combining scaffold and stem cells technologies to develop and study cornealised mimetic constructs.

We are also currently establishing manufacturing processes to take emerging technologies into the clinic (read more).

 

Decellularised corneas

Up to 25% of donated human corneas, and 9 out of 10 potential donors are rejected for transplantation for reasons unrelated to structural quality. If decellularised and processed in the appropriate way, many of these corneas could be recycled for transplantation and research purposes. Recycling corneas overcomes the major engineering and costly challenge of recreating the corneal architecture artificially. The native cornea posses all the natural biological cues for effective regeneration that any manufactured scaffold could never mimic.

We are currently developing novel techniques for effective decellularistion that will allow cycling of human corneas at a manufacturing level. We aim to produce a corneal-derived scaffold that is safe and effective for human transplantation (read more).

 

3. Protection against infection

Involvement of antimicrobial peptides in ocular surface defence

Antimicrobial peptides are natural analogues of antibiotics produced by the body. The body produces a broad profile of different antimicrobial peptides constitutively in health to prevent infection, and then in disease to combat infection. The ocular surface is continuously exposed to the harsh external environment and is continually presented with invading pathogens. Antimicrobial peptides are believed to represent an important first line of host defence against invading microorganisms, which is highly successful until this system is compromised.

Academic Ophthalmology pioneered research into the field of ocular antimicrobial peptides, and has profiled the spectrum of expression at the ocular surface, including the highly novel beta defensing 9. We have made a demonstrable contribution to the understanding of how the infecting organism determines the profile of expression and therefore how a certain profile of expression represents specific bacterial, viral and acanthamoebal infections. We have elucidated the underpinning signaling mechanisms involved in expression of key peptides including RNase 7, Psioriasin and Beta Defensin 9 and how these mediate the ocular immune responses to involve inflammation.

We are currently investigating, at the translational level, the therapeutic potential of the most important ophthalmic antimicrobial peptides in combatting sight-threatening infections (more about our research).

 

4. Ocular anatomy

Corneal nerves

The effect of cutting and laser ablation of the cornea in various refractive surgery procedures has drawn much attention to the corneal innervation in recent years. Disease and insults to the ocular surface is also known to compromise the nerve architecture. The loss of corneal innervation is related to long-term epithelial defects and pain.

Using in vivo confocal microscopy and histological staining we have redefined the normal architecture of corneal nerves and have made considerable progress in understanding how diseases and surgery affects this. We are able to now assess and classify nerve damage in living patients.

 

Dua’s layer

In 2013 Professor Dua’s clinical research team described a previously undiscovered layer in the cornea. It is hypothetically 15 micrometres (0.00059 inches) thick, the fourth layer from the front, and located between the corneal stroma and Descemet's membrane. Despite its thinness, the layer is very strong and impervious to air. It is strong enough to withstand up to 2 bars (200 kPa) of pressure.

The layer may help surgeons improve outcomes for patients undergoing corneal grafts and transplants. During surgery, tiny air bubbles are injected into the corneal stroma in what is known as the "big bubble technique". Sometimes the bubble bursts, damaging the patient's eye. If the air bubble is injected under Dua's layer instead of above it, the layer's strength could reduce the risk of tearing.

 

Limbal epithelial crypt

Regeneration of the corneal epithelium is maintained by stem cells, which are believed to reside in the limbal region, defined as the outer periphery of the cornea bordering with the white sclera. The precise location of limbal stem cells is uncertain.

Academic Ophthalmology discovered a follicle like anatomical structure in the deep stroma sparsely located in limbus. Extensive characterization of these structures revealed cells residing within demonstrated morphological and marker characteristics of stem cells.

We have now fully characterised the gene profile of these and others cells of the cornea and demonstrate the limbal epithelial crypt contains highly quiescent cells enriched in stem cell properties. Using novel stem cell markers identified in this study we are currently developing techniques to isolate and expand these cells for basic research and translational exploitation purposes.

 

Links

Funders

 

Contacts

Professor Harminder Dua is Head of Academic Opthalmology and the president of the Royal College of Ophthalmologists.

Dr Andrew Hopkinson is the lead scientist and the founder of the Nottingham Centre for Eye Research (NCER).

 

 

PhD opportunities

 

 

 

 

Academic Ophthalmology

The University of Nottingham
Queen's Medical Centre, B Floor, Eye and ENT
Nottingham, NG7 2UH


telephone: +44 (0) 115 97 09796
email:eunice.doyle@nottingham.ac.uk