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Vision Research Program in neurodegenerative diseases

The visual system is an integral part of the central nervous system (CNS) and, as such, is susceptible to the damage that CNS incurs during the progression in many neurodegenerative diseases. The involvement of the visual system has been long recognized in several neurodegenerative diseases, such as Alzheimer's disease, traumatic brain injury, stroke, Parkinson's disease, multiple sclerosis and others. However, many aspects of this involvement are still understudied and deserve further investigation.

Thus, the primary goal of the Vision Research Program at The Roskamp Institute is to elucidate some of the mechanisms of damage at all levels of the visual system (eye/retina, optic nerve, visual cortex) in models of neurodegenerative diseases and to identify new therapeutic approaches with the potential to limit or even reverse the consequences of this damage.


Our goal is to characterize the physiological, morphological and biochemical consequences of mild repeated TBI for the visual system under controlled conditions in models of the disease and to develop treatments focused on shortening the recovery period from TBI or, in more severe cases - slowing down or even prevention of the associated visual deficits. Traumatic brain injury (TBI) occurs when a sudden external mechanical force traumatically injures the brain. TBI can be classified by severity as mild, moderate and severe, and the severity is correlated with the duration of the symptoms and the prognosis for recovery. It has been shown that even a mild TBI can be risk factor for neurodegeneration (Gavett et al. 2010) and that neurodegenrative processes can be triggered many years after even a single TBI (Johnson et al. 2012).

Vision impairment as a result from TBl has been recognized since ancient times. The Hippocratic Corpus, collection of medical works from ancient Greece, mentions concussion, later translated to commotio cerebri, and discusses loss of speech, hearing and sight that can result from "commotion of the brain" (Masferrer et al. 2000). In modern times, visual complaints are considered an important part of TBI symptomatology; self-reported visual complaint can be found in up to 75% of the patients (Cockerham et al. 2009). Light sensitivity, blurred vision, difficulty fixating and difficulty reading are only few of the symptoms reported, which can last from few weeks to many years, and, in some cases, can lead to permanent visual impairment.

 

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Repeated occurrence of TBI, even if only as mild, can result in cumulative sensory and cognitive deficits. Visual symptoms can be the same as after single TBI, but they could last longer and could interfere more with daily activities.
In some cases, patients may not be even aware that they have visual function deficits (especially peripheral visual field defects) and, thus, the true extent of visual impairment after repeated mild TBI may be underestimated.

 

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Research has shown that the optic nerve can be affected after TBI even without a direct injury to the eye or the orbit. Clinically, this is referred to as indirect traumatic optic neuropathy (ITON) and it can occur in up to 5% of the patients after TBI, although good epidemiological studies are lacking and it is likely that some effect on the optic nerve structure and function, especially when subclinical, are more prevalent.

Our goal is to characterize the physiological, morphological and biochemical consequences of mild repeated TBI for the visual system under controlled conditions in models of the disease and to develop treatments focused on shortening the recovery period from TBI or, in more severe cases - slowing down or even prevention of the associated visual deficits.

Alzheimer disease (AD) is a progressive, age-related, debilitating neurodegenerative condition and a growing public health problem in the developed world. Presently, no effective treatment is available and the median life expectancy is between 7 to 10 years for patients diagnosed in their 60s and early 70s, or less, if they are diagnosed later. The nature of this chronic, debilitating disease is such that the burden for the society is enormous. In the US, total health and long-term care payments for people with AD and other dementias in 2012 were estimated at $200 billion. To this cost the contributions of unpaid caregivers should be added; for 2011, an estimated 15 million Americans (80% of which are family caregivers) provided 17.4 billion hours of care to persons with AD and other dementias, valued at nearly $210 billion (Alzheimer's Association 2012).

Vision Problems with AlzheimersThe visual system is clearly affected in AD, although some important details require further investigation. Thus, the visual cortex (the part of the brain responsible for primary analysis of the visual information) seems to present with neuronal loss in AD. Several brain nuclei involved in the visual processing (SC, SCN and the visual pulvinar) also appear to be affected. Although optic neuropathy in AD seems to be clearly established by now, some important details are still elusive, like the predominant involvement of thick or thin axons. Recent findings confirm the longstanding suspicion that the retina is also involved, although here, again, some important details, like the number and type of neuronal cell loss and the characteristics of the ongoing degeneration are uncertain.

The goal of our research is to characterize the physiological, morphological and biochemical consequences of AD progression for the visual system in models of the disease and to develop treatment options for slowing down or prevention of associated visual function deficits.

Ophthalmic neurodegenerative diseases, such as retinitis pigmentosa, age-related macular degeneration, Stargardt disease, glaucoma and others, share many pathological mechanisms with neurodegenerative processes occurring in the Central Nervous System (CNS). Therefore, therapeutic or diagnostic approaches against inflamation being tested in the CNS could be useful when applied in ophthalmic conditions. The vision research program's secondary goal is to look into new therapeutic and diagnostic possibilities for ophthalmic degenerative diseases based on CNS knowledge and experience.

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Dr. Rad Tzekov joined the Roskamp Institute in 2011 with extensive pre-clinical and clinical experience in academic and pharmaceutical industry settings. His main area of expertise is developing, characterizing and using models of retinal and optic nerve diseases to improve the available diagnostic and therapeutic options. He also conducts advanced clinical visual function testing at the USF Eye Institute in Tampa, FL.


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