Retinoblastoma is a childhood retinal tumor usually affecting children one to two years of age. Although rare, it is the most common malignant tumor of the eye in children. Left untreated, retinoblastoma can be fatal or result in blindness. It has also played a special role in understanding cancer, because retinoblastomas have been found to develop in response to the mutation of a single gene – the RB1 gene – demonstrating that some cells are only a step away from developing into a life-threatening malignancy.

David E. Cobrinik, MD, PhD, of The Vision Center at Children’s Hospital Los Angeles (CHLA), together with colleagues at Memorial Sloan-Kettering Cancer Center, has answered the long-standing question of why mutations to the RB1 gene primarily cause tumors of the retina and not of other cell types. His study – which could reveal new cellular signaling pathways relevant to retinal development, cancer development, and ultimately, the development of novel therapies – is published in this week’s early on line issue of the journal Nature.

“These findings significantly advance our understanding of cancer, not only because they solve the RB riddle, but also because they more generally imply that cancers can develop through the collaboration between a cancer-causing mutation – in this case, inactivation of the RB1 gene – and cell type-specific circuitry,” said Cobrinik, who also an investigator with The Saban Research Institute of CHLA and associate professor of Ophthalmology at USC Eye Institute, Keck School of Medicine at the University of Southern California.

The RB1 gene encodes a tumor suppressor protein, referred to as Rb, which prevents excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. If both alleles of the RB1 gene are mutated early in life, the Rb protein is inactivated, resulting in development of retinoblastoma cancers. (While the Rb protein regulates proliferation in many cell types, only cells in the retina routinely form cancers when the function of the RB1 gene is lost.)

Cobrinik and colleagues discovered that retinoblastomas originate in cone photoreceptor precursors, and their study explains why retinoblastomas originate in these precursor cells. Cone cells, or cones, are one of the two types of photoreceptor cells in the retina, and are responsible for color vision. A cone precursor is an immature cone cell which is not yet fully differentiated.

The study indicates that cone precursors prominently express key, cancer-related proteins that enable proliferation and suppress apoptosis, or programmed cell death. Meanwhile, the role of the Rb protein is to hold back such proliferation – which means that the loss of Rb alone is sufficient to allow unchecked cell proliferation, causing retinoblastomas to form.

“We showed that the cone precursors’ normal developmental program collaborates with RB1 mutations to deregulate cell growth,” Cobrinik explained. “In other words, loss of the RB1 gene results in abnormal proliferation because the cone precursor cells lack a self-monitoring ‘surveillance system’ – which would normally cause aberrantly proliferating cells to undergo apoptosis. Instead, cells are able to divide uncontrollably and eventually become cancerous.”

http://www.medicalnewstoday.com/releases/283008.php

Does a distinctive mechanism work in the brain of congenitally blind individuals when understanding and learning others’ gestures? Or does the same mechanism as with sighted individuals work? Japanese researchers figured out that activated brain regions of congenitally blind individuals and activated brain regions of sighted individuals share common regions when recognizing human hand gestures. They indicated that a region of the neural network that recognizes others’ hand gestures is formed in the same way even without visual information. The findings are discussed in The Journal of Neuroscience (July 23, 2014 electronic edition).

Our brain mechanism perceives human bodies from inanimate objects and shows a particular response. A part of a region of the “visual cortex” that processes visual information supports this mechanism. Since visual information is largely used in perception, this is reasonable, however, for perception using haptic information and also for the recognition of one’s own gestures, it has been recently learned that the same brain region is activated. It came to be considered that there is a mechanism that is formed regardless of the sensory modalities and recognizes human bodies.

Blind and sighted individuals participated in the study of the research group of Assistant Professor Ryo Kitada of the National Institute for Physiological Sciences, National Institutes of Natural Sciences. With their eyes closed, they were instructed to touch plastic casts of hands, teapots, and toy cars and identify the shape. As it turned out, sighted individuals and blind individuals could make an identification with the same accuracy. Through measuring the activated brain region using functional magnetic resonance imaging (fMRI), for plastic casts of hands and not for teapots or toy cars, the research group was able to pinpoint a common activated brain region regardless of visual experience. On another front, it also revealed a region showing signs of activity that is dependent on the duration of the visual experience and it was also learned that this region functions as a supplement when recognizing hand gestures.

As Assistant Professor Ryo Kitada notes, “Many individuals are active in many parts of the society even with the loss of their sight as a child. Developmental psychology has been

advancing its doctrine based on sighted individuals. I wish this finding will help us grasp how blind individuals understand and learn about others and be seen as an important step in supporting the development of social skills for blind individuals.”

http://www.medicalnewstoday.com/releases/282166.php

It is widely accepted that age-related macular degeneration (AMD) is the most common cause of visual impairment and blindness in industrialized countries. However, it is questionable whether it can continue to be defined as a disease in people in their 50s and beyond. Investigations to determine the incidence of age-related macular degeneration undertaken as part of the Gutenberg Health Study of the University Medical Center of Johannes Gutenberg University Mainz (JGU) have shown that even persons under the age of 50 years may be affected by an early form of the eye disease. Just under 4 percent of the 35 to 44-year-old subjects in the population-based study were found to be suffering from AMD.

In order to identify the age- and gender-specific incidence of AMD, the research team of the Department of Ophthalmology at the Mainz University Medical Center led by Dr. Christina Korb, PD Dr. Alireza Mirshahi, and Professor Norbert Pfeiffer assessed the status of the ocular fundus of 4,340 participants in the Gutenberg Health Study. Evaluated were vascular structure, the head of the optic nerve, and the macula of the eye, which is the point of sharpest vision. The results in general documented that the incidence of AMD increases with age. However, the researchers also discovered to their surprise that even persons under the age of 50 years can already be affected by early stage AMD. In the age group of 35- to 44-year-olds, 3.8 percent of the subjects in the Gutenberg Health Study were found to be suffering from the disease. The findings of the Mainz researchers thus contradict the current assumption that age-related macular degeneration only occurs in the section of the population that is over 50 years old.

With the help of their findings, the researchers were also able to gain insights into how frequently the various forms of age-related macular degeneration occur. On average, about 12 percent of the examined 35- to 74-year-olds had early stage AMD, but only 0.2 percent of the study participants exhibited symptoms of late stage AMD, which is often associated with severe visual impairment. “Our research shows that age-related macular degeneration can already occur much earlier than previously thought. This means there may also be possible consequences with regard to the screening examinations for these diseases,” concluded Dr. Christina Korb.

Age-related macular degeneration leads to loss of visual acuity. The cause is damage to the cells in the region of the central retina also known as the “yellow spot.” There is still insufficient information on the annual number of individuals who develop AMD and the Mainz-based researchers hope to be able to remedy this with the help of their next project. As the Gutenberg cohort was subjected to a follow-up examination five years after inclusion in the study, the research group has now access to more relevant and reliable data. “The prospective design of the study, in combination with the availability of interdisciplinary research data, should make it possible for us to identify risk factors for the development of late forms of AMD in our cohort. We are looking forward with some excitement to the results,” explained the team. The objective is to reveal, for the first time, the incidence of AMD across the whole population of Germany.

The Gutenberg Health Study (GHS) is an interdisciplinary, population-based, prospective, monocenter cohort study, which has been conducted at the Mainz University Medical Center since 2007. Cardiovascular diseases,cancer, eye diseases, metabolic disorders as well as immune system and mental disorders are being investigated as part of the study. The goal of the study is to improve the individual risk prediction for these diseases. To this end, lifestyle, psychosocial factors, environment, clinical laboratory parameters, and the severity of any subclinical disorder are being taken into consideration. A comprehensive biorepository is being developed so that molecular biological investigations can be conducted. During the baseline visit, 15,010 participants aged 35 to 74 years were invited to participate in a 5-hour examination program at the study center. This was followed by a computer-assisted telephone interview (CATI) using a standardized questionnaire and the assessment of diseases and health problems after 2.5 years. All endpoints will be subjected to extensive validation. In April 2012, a detailed follow-up examination of participants similar to the baseline examination was conducted at the center five years after their inclusion in the study. The aim is to continue to monitor the cohort and conduct further tests.

http://www.medicalnewstoday.com/releases/279917.php

Picture courtesy of lighthouse.org