Genetics And Lifestyle Interact To Increase Risk For Age-Related Blindness

The interplay between genetic predisposition and exposure to modifiable risk factors can multiply the risk for age-related macular degeneration, according to a report in the January issue of Archives of Ophthalmology, one of the JAMA/Archives journals.



Age-related macular degeneration (AMD) can cause blindness and is known to have both genetic and environmental risk factors, according to background information in the article. Researchers have previously found that a mutation in the gene for complement factor H (CFH) is associated with AMD, as is a mutation in the gene LOC387715. Because these mutations are common in the white population, it is likely that other factors--such as obesity and smoking--may modify the risk for AMD. "Elucidation of these modifying factors may increase understanding of disease pathogenesis and suggest lifestyle changes that may prevent AMD or delay the disease onset in carriers of predisposing genetic variants," the authors write.



Debra A. Schaumberg, Sc.D., O.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues compared 457 men and women with AMD (cases) to 1,071 controls who were the same age and sex as the cases but did not have AMD. All of the individuals were part of either the Nurses' Health Study, a large examination of female registered nurses who were between the ages of 30 and 55 years in 1976, or the Health Professionals Follow-up Study, which includes male U.S. health care professionals who were ages 40 to 75 in 1986. The participants were examined when they enrolled in the studies and completed a follow-up questionnaire every two years; average age at AMD diagnosis was 68.7 years.



Blood samples were also collected for a genetic analysis. Information about CFH was available for 437 AMD cases and 1,015 controls, while information about LOC387715 was available for 445 AMD cases and 1,041 controls. Compared with those who had two normal copies of each gene (alleles), those who had two mutated alleles of both genes were 50 times more likely to develop AMD.



Individuals who carried two mutant alleles of the CFH gene and were not obese were four times as likely as non-obese individuals with two normal alleles to develop AMD. If those individuals also smoked, their risk was 8.69 times as great as non-smoking non-carriers. If individuals were obese and carried two mutant alleles of the CFH gene, their risk increased 12 times as compared with non-obese non-carriers. For LOC387715, risk increased by 6.33 times for those with two mutated alleles who did not smoke and 22.47 times for those with two mutated alleles who did smoke. The genetic risk factors were not affected by other risk factors associated with AMD, including regular aspirin use, fruit intake, fatty acid ratios or alcohol consumption.



Because these genetic mutations are so common, some have questioned the utility of widespread screening for AMD risk, the authors write. "The existence of interactions with modifiable lifestyle factors may provide further impetus for screening individuals who are at potentially greater risk [for AMD], for example, cigarette smokers or the obese," they continue. "Knowledge of the substantial risk of AMD among individuals homozygous for either or both of these major AMD-associated variants might help motivate these individuals to stop smoking, lose weight, modify other risk factors and have regular eye examinations."

NanoViricides, Inc. Eye Drug Testing Has Begun

NanoViricides, Inc. (OTC BB: NNVC.OB) (the "Company"), reported today that testing of its topical eye drops drug candidate has begun at two different, independent facilities.


Testing of this broad-spectrum, topical, eye drug candidate by a major pharmaceutical company ("Party") is now in progress. The Company had previously announced in March that it had signed a Material Transfer Agreement with this Party. In addition, the Company is also evaluating this drug candidate against herpes keratitis of the eye at Thevac, LLC, a spin-off of the Louisiana State University (Study Director, K. G. Kousoulas, PhD).


The testing at the two facilities will independently evaluate performance of this drug candidate against several types and strains of many different viruses that cause keratitis or conjunctivitis of the eye. Cell culture studies as well as animal studies with different animal models have been planned.


"Execution of the material transfer agreement (MTA) is a step towards a potential licensing agreement," said Eugene Seymour, MD, MPH, CEO of Nanoviricides, Inc. The terms of the agreement do not allow the disclosure of the identity of the Party or the exact terms of the MTA.


HSV and some adenoviruses cause most of the cases of keratitis, a serious infection of the cornea. Importantly, HSV infection can lead to corneal scarring that may necessitate corneal transplantation. In addition, some adenoviruses cause a majority of conjunctivitis cases ("pink eye"). The remaining cases of conjunctivitis, caused by bacteria, are treatable with topical antibiotics. Currently, there are no effective treatments for viral diseases of the exterior portion of the eye.


The Company has already demonstrated strong efficacy against an adenovirus-caused external eye disease called epidemic kerato-conjunctivitis (EKC). Rapid clinical improvement in the treated animals was reported by independent researchers who tested the effects of the nanoviricides drug candidate against adenoviral EKC. Based on computer modeling, the Company believes that the broad-spectrum nature of the ligand used in this nanoviricide should enable it to be effective against HSV.


The total market for all forms of viral conjunctivitis/keratitis is estimated to be in the billions of dollars. The incidence of severe herpes (HSV) keratitis is estimated to be 250,000 cases per year in the USA. In Japan, where EKC is a reportable disease, it is estimated that there are at least one million cases per year. The number of cases of non-specific conjunctivitis (pink eye) is considered to be far greater, possibly into tens of millions in the US, and into hundreds of millions worldwide.

Source

NanoViricides

Genetic Modifier In Usher Syndrome Will Lead To Better Diagnosis

Usher syndrome (USH), an inherited condition involving both hearing and vision loss, is not a simply recessively inherited disease, a scientist told the annual conference of the European Society of Human Genetics (Saturday 12th June). Dr. Hanno Bolz, Associate Medical Director of the Bioscientia Centre for Human Genetics, Ingelheim, Germany, and active in teaching and research at the University Hospital of Cologne, will say that his team's research challenges the traditional view that USH was inherited as a single gene disorder, and shows that it may result from at least two different genetic mutations. This could lead to more accurate diagnosis of this condition, which is responsible for up to 10% of all cases of childhood deafness and 50% of all deaf/blindness in adults.



Some USH patients have only one mutant copy of an Usher gene, which in itself is insufficient to explain a recessive disease, and there is often an unexplained variability of the visual characteristics of the condition, even between close family members. Dr. Bolz's team, including scientists from Cologne University, Germany and zebrafish researchers from the University of Oregon, USA, decided to look for additional USH genes and genetic modifiers that could be involved in disease causation.



"We became interested in researching sensory diseases such as Usher syndrome because they can be very debilitating and affect people at a young age", said Dr. Bolz. "Despite extensive research into USH, there is currently no effective treatment for it."



Apart from linkage studies of recessive disease, where a particular trait or disease characteristic is traced within a family, another way of identifying genes linked to disease is to analyse genes that encode proteins which are similar to the proteins involved in the disorder being studied. Using a genome-wide database search, the team identified a gene, PDZD7, which encoded a protein with striking similarity to the proteins whirlin and harmonin, both known to be involved in USH.



"We found that some patients with only a single mutation of the gene responsible for the condition, GRP98, also had a mutant copy of PDZD7, and that this gene interacts with proteins involved in USH", said Dr. Bolz. "We were able to validate these findings in transgenic zebrafish, and to show that PDZD7 localises to cilia, thus providing further confirmation that USH is a retinal ciliopathy."



Cilia are antenna-like protuberances that project from cells and are often involved in sensory activity such as vision, hearing or smell. Genetic mutations can affect their proper functioning, and these defects in turn affect critical signalling pathways essential to cell development. As a result, cilia defects are involved in many diseases which produce multiple symptoms.



Diagnosis of USH is complicated, the scientists say. At present it is normally related to clinical symptoms, such as childhood hearing impairment and the vision disease retinitis pigmentosa in the first or second decade of life. Retinitis pigmentosa affects the layer of light-sensitive tissue in the retina and vision loss occurs as the light-sensing cells gradually deteriorate, causing blind spots which eventually merge to produce tunnel vision and sometimes total blindness.



"When hearing and visual loss are both present, the most likely diagnosis is Usher syndrome", said Dr. Bolz. "More precise genetic diagnosis is essential, but the genes are large and not easily accessible to genetic testing. However, by considering clinical data of the patient and the background of his/her family - ethnicity, for example - one can apply efficient testing strategies. For the parents of a deaf child, it would be advantageous to be aware of the retinal degeneration that will occur later on.



"Research on new Usher genes must therefore be translated quickly into genetic testing in order to aid parents to choose appropriate therapies to diminish the later consequences of the disease," he said. The decision to opt for a cochlear implant, for example, could be influenced by the knowledge as to whether the causative mutation is in a gene for isolated deafness or in a USH gene.



"We believe that our work may serve as a paradigm for the future", said Dr. Bolz. "In many recessive diseases, variability of disease characteristics is the rule rather than the exception, and in most cases this phenomenon is unexplained. With advances in new sequencing techniques that permit simultaneous analysis of several genes, we will need to interpret variants in all Usher genes in a patient, not only in one. Two hits in a single Usher gene may explain the disease in a patient, but not its variability. Our research is a step on the road to understanding that variability and to being able to provide an accurate prognosis of disease progression."



Source:

Mary Rice

European Society of Human Genetics

Inhaled And Oral Steroid Use Impacts Cataract Risk

A study conducted by the Centre for Vision Research, University of
Sydney, Australia, examines how steroid (corticosteroid) use relates
to risks for cataract,b the clouding of the eye's lens that leads to
reduced vision and blindness, if untreated.


Many people with asthma
rely on inhaled, and sometimes oral, steroids, as do people with
chronic obstructive pulmonary disease (COPD). This population-based
study, a cohort of the Blue Mountains Eye Study, followed 3,654
Australians, aged 49 years or older, five and 10 years after initial
(baseline) examinations conducted between 1992 and 1994. This
timeframe was needed to assess the long-term impact of steroid use on
cataracts, which develop slowly over years. Based on their findings,
the researchers suggest that more judicious prescription of combined
inhaled and oral steroids may decrease cataract risk for asthma
patients.



"Our findings could mean that combined steroid use, when it results
in high cumulative dosage over relatively long periods, increases
risks for two types of cataract," said lead researcher, Jie Jin Wang,
MMed, PhD, Centre for Vision Research. "When clinicians prescribe
both steroid forms, the cumulative, combined dose should be
considered. Also, recent clinical trials indicate that combined
steroids are not more effective than inhaled steroids alone in
treating asthma." He added that further investigation is needed to
determine whether asthma plays a role in nuclear cataract
development.



Elevated cataract risks were found only in patients who, at the time
of their baseline exams, had ever used inhaled steroids, had also used
oral steroids for at least one month, and had no cataracts. Patients
at highest risk for two types of cataract were those defined at
baseline as "current users" of both steroid forms; although this was
a small group, follow up exams found that nearly all of them
developed cataracts. Of seven current user patients, five had used
either steroid form for more than five years, and four of the five
developed posterior subcapsular cataract (PSC). Three additional
current user patients developed nuclear cataracts. In nuclear
cataracts the center of the lens is obscured, and in PSC the cataract
develops in the rear area of the lens. Earlier research had
established a higher risk for PSC in oral steroids users.


April 2009 Issue of Ophthalmology.


About the American Academy of Ophthalmology



AAO is the world's largest association of eye physicians and surgeons
-- Eye M.D.s -- with more than 27,000 members worldwide. Eye health
care is provided by the three "O's" -- opticians, optometrists and
ophthalmologists. It is the ophthalmologist, or Eye M.D., who can
treat it all: eye diseases and injuries, and perform eye surgery.

Source
American Academy of Ophthalmology

Prospects Grow For Blindness Recovery, Australia

Prospects for recovery of lost vision have brightened with the release of new scientific findings showing that the use of gentle near infra-red light can reverse damage caused by exposure to bright light, up to a month after treatment.


The Vision Centre's Dr Krisztina Valter and doctoral researcher Rizalyn Albarracin have successfully demonstrated recovery of vision cells in the retina following near infra-red treatment applied after damage was sustained.


Their advance has raised hopes for the development of a practical, low-cost and painless treatment for damaged eyes - including for patients suffering from dry macular degeneration (dry AMD), now the most common cause of blindness in developed countries.


The finding, made using an animal model, builds on the evidence the team has established showing that pre-treatment of eyes with near infra-red can help to minimise damage caused by bright light and enhance recovery.


"Macular degeneration is responsible for around a half of the cases of blindness in Australia. The dry form, for which there is still no cure, accounts for 80-90 per cent of cases," says Dr Valter, of The Vision Centre and Australian National University. "Our research shows clear evidence of recovery of vision cells from light damage, a good model for what happens in dry AMD."


"Given the very high costs of blindness to any economy, it is encouraging to know that there is a simple, affordable technology in prospect which could help to reduce it."


Ms Albarracin said that treating the retina with just a few minutes exposure to soft near-infra-red light a day for less than a week had produced a remarkable recovery in damaged photoreceptors (vision cells) which ordinarily would have died.


"You only have one set of vision cells, so if you lose them they can never be replaced. When they are damaged or stressed, they shut down and gradually die or kill themselves. You get a horrible 'hot spot' of dying cells in your retina, which gradually spreads out in a sort of domino effect until your vision is gone," she explains.


"We have found that treating the cells before, during or even after light damage raises their protective factors and resistance to stress, and slowly allows their vision function to return. The retina looks really sick - but then it just bounces back. It's almost a kind of a resurrection."


Since only a few people know in advance they may suffer vision damage from bright light and can be pre-treated, knowing that near infra-red treatment soon after injury also causes the cells to heal well is an important step towards developing a practical therapy for people who are losing their sight either from injury or slow-onset conditions.


The technique could potentially be used to treat a wide range of forms of vision loss, including dry AMD, retinitis pigmentosa, inflammation of the retina and some diseases of the optic nerve, the researchers say.


"We're using an array of small LEDs (light emitting diodes) that have been tuned to produce near infra-red light at a particular wavelength. These are fairly cheap, making a potential treatment very affordable - especially when you consider the overall costs of blindness," Dr Valter says.


She says that the evidence yielded by the latest research is now so persuasive that the team could move to human trials this year, if they can secure a clinical partner.


"Near infra-red therapy is very benign and involves no discomfort to the patient. It is already approved by the US Food and Drug Administration for use in sports medicine, for hair loss and so on - so developing a novel therapeutic application for the eyes is likely to be less complex and protracted than, say, developing a new drug," she adds.


Their paper "Photobiomodulation protects the retina from light-induced photoreceptor degeration," by Rizalyn Albarracin, Janis Eells and Krisztina Valter appears in the latest issue of the journal Investigative Ophthalmology and Vision Science


The Vision Centre is funded by the Australian Research Council as the ARC Centre of Excellence in Vision Science.


Source:

The Vision Centre

Australian First To Save Sight

A new system of storing eye tissue, to be launched on Tuesday 14 February at the Lions Corneal Donation Service (LCDS), will help save the sight of hundreds of Victorians a year by extending the time between donation and needing to perform the transplant.



Thanks to the new facilities, LCDS can now store corneas at human body temperature levels (34C) for up to a whole month. Previously, corneas were held at low temperatures and had to be transplanted within one week of the donation.



Dr Graeme Pollock, Director of the Lions Corneal Donation Service, said no other corneal donation facility in Australia offered this kind of service.



"Our ability to store the corneas for longer means reduced surgery postponements and waiting time for people living with vision loss," Dr Pollock said.



Corneal recipient Dorothy O'Kane, 61, welcomed the news after initially missing an opportunity for a corneal transplant when she was on holiday in South Australia.



"If this system had been in place at that time I could have come back and the cornea would have still been there for me," Mrs O'Kane said.



Mrs O'Kane, who eventually underwent a transplant in July 2005, said the improvement in her sight was remarkable, enabling her to enjoy life to the full.



"I can even see the freckles on my grandson's nose."



The new system is being launched in the lead up to Organ Donor Awareness Week to encourage people to consider corneal donation to save the sight of others.



The Lions Corneal Donation Service will be officially opened with a press conference at 10.15am on Tuesday 14 February 2006, 7th Floor Smorgan Family Wing, The Royal Victorian Eye and Ear Hospital, 32 Gisborne St, East Melbourne (due to renovations please enter via Morrison Place).



Interviews will be available with corneal recipient Dorothy O'Kane (61) and Iola Matthews (62), who is due to undergo her first corneal transplant on Thursday.



There is also an opportunity to film an operation of a corneal transplant at the Eye and Ear hospital on Tuesday following the opening.







The Lions Corneal Donation Service, supported by the Victorian and New South Wales Lions Foundation is a division of the Centre for Eye Research Australia is housed at The Royal Victorian Eye and Ear Hospital in East Melbourne.



If you want to donate your corneas you must tell your family and register on the organ donor register. For information on donating your corneas please contact Graeme Pollock on +61 399 298 709. We urge Australia to consider giving the gift of sight and donate your corneas.



Contact: Romy Johnston

romyjunimelb.edu.au

EYE RESEARCH AUSTRALIA FOUNDATION

2009 President's Award Presented To Rohit Varma, MD

In ceremonies on January 28 at the legendary Palace Hotel in San Francisco, Glaucoma Research Foundation President and CEO Thomas M. Brunner presented The President's Award to Rohit Varma, MD. Dr. Varma is Professor of Ophthalmology and Preventive Medicine, and Director of the Glaucoma Service at the USC Keck School of Medicine.


The Glaucoma Research Foundation President's Award acknowledges exemplary volunteer leadership. Dr. Varma's recent Los Angeles Latino Eye Study (LALES), confirming that Latinos are among the highest at risk for glaucoma, is widely regarded as the definitive research on this subject. Inspired by Dr. Varma's urgent call to action, and with funding from Allergan, the Glaucoma Research Foundation last year hosted Ver Es Poder (Seeing is Empowering), a Glaucoma Awareness Day at the Delhi Center in Santa Ana. More than 200 people, including families and people of every age, lined up to hear the opening ceremony and participate in a comprehensive glaucoma screening. By the end of the day, more than 350 people had participated.


Dr. Varma's personal leadership in Ver Es Poder - giving previews of his research findings to community groups, mobilizing several Spanish-speaking physicians in his team at Doheny Eye Institute to volunteer their time in the screenings - set the highest example. His generosity of spirit not only inspired others to make glaucoma awareness a personal priority, but also showed that an entire community could rally around that cause.

Glaucoma Research Foundation