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Targeted X-Ray Treatment of Mice Prevents Glaucoma

By MedImaging International staff writers
Posted on 05 Apr 2012
Researchers have demonstrated that a single, targeted X-ray treatment of a single eye in young, glaucoma-prone lab mice provided that eye with apparently life-long and typically complete protection from glaucoma.

In research published March 19, 2012, in the Journal of Clinical Investigation, Gareth Howell, PhD, Simon John, PhD, a professor at the Jackson Laboratory (Bar Harbor, ME, USA), and colleagues also used advanced genomics applications to discover some of the very first pathways to change during glaucoma in these mice. The first pathway they identified to change suggests a critical process that could be responsible for the earliest damage that glaucoma inflicts on the optic nerve.

Glaucoma, a leading cause of blindness, affects more than four million people in the United States alone, at least half of whom do not even know they have the disease. Current treatments target intraocular pressure elevation, the best-known risk factor for glaucoma. However, blindness-inducing damage to retinal ganglion cells and the optic nerve can occur in patients with normal intraocular eye pressure. Earlier detection and better treatments could therefore have a powerful impact on preventing blindness due to glaucoma.

Approximately a decade ago, the John lab made the remarkable discovery that just a single dose of whole-body irradiation along with bone marrow transfer conferred an unprecedented protection against glaucoma. Ninety-six percent of treated eyes had no glaucoma a year later compared to only 20% of control eyes.

Although this result was unexpected, there is some evidence that radiation may protect from human glaucoma. Epidemiologists who tracked Japanese survivors of the atomic bombings in World War II had noticed that exposure to radiation increased the incidence of thyroid and other cancers but seemed to provide protection against glaucoma.

The John labs’ new demonstration that irradiation of just one eye is protective, and at lower doses than they previously published, raises the possibility of using very controlled localized radiation of just the eye to prevent human glaucoma.

Further research in other animal models to assess protection as well as safety and effectiveness is necessary before attempting human treatments. However, as the authors concluded in their article, “Given both the robust and long-term efficacy of a single dose of X-ray radiation in preventing cellular entry into the optic nerve and retina, it will be important to further evaluate the use of X-rays for preventing glaucoma.”

The study demonstrated that in response to early tissue stresses, a type of immune cells called monocytes, enter the optic nerve and retina in glaucoma. These monocytes express damaging molecules that appear critical for nerve damage in glaucoma. The entry of these cells is controlled in part by endothelial cells that line blood vessels. Radiation treatment appears to change how these endothelial cells respond to the early tissue stresses and affect the entry of the monocytes into the optic nerve and retina.

“While more work is needed to fully understand how the radiation confers long-term protection,” Dr. Howell said, “radiation appears to hinder the adhesion and migration of monocytes into the areas of the eye prone to nerve damage.” This finding strongly implicates the entry of cells into the eye as a key component of the nerve damage that leads to blindness. It also suggests vision may be maintained in eyes with high intraocular pressure by treatments that block the entry of monocytes into the eye.

The Jackson Laboratory is an independent, nonprofit biomedical research institution and US National Cancer Institute (Bethesda, MD, USA)-designated cancer center based in Bar Harbor, Maine, with a facility in Sacramento, CA, USA, an institute for genomic medicine planned in Farmington, CT, USA, and a total staff of approximately 1,400. Its goal is to uncover the genetic basis for preventing, treating, and curing human disease, and to enable research and education for the global biomedical community.

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87 (!!!!! 2584.9342346191): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (125.16975402832): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (66.995620727539): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (123.97766113281): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (51.975250244141): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (61.03515625): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (190.97328186035): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (185.96649169922): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (!!!!! 2524.8527526855): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (255.10787963867): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (!!!!! 4171.8482971191): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (443.93539428711): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (!!!!! 3947.9732513428): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (118.97087097168): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (!!!!! 6671.1902618408): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
105 (128.98445129395): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
106 (113.96408081055): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (636.10076904297): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 3064.8708343506): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
109 (532.15026855469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
110 (73.909759521484): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (!!!!! 2115.9648895264): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (!!!!! 1197.0996856689): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (!!!!! 1110.0769042969): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (375.03242492676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
115 (144.00482177734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
116 (!!!!! 2646.2078094482): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
117 (762.939453125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
118 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
119 (252.96211242676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
120 (464.91622924805): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
121 (65.803527832031): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
122 (!!!!! 2284.049987793): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 64359.903335571): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (!!!!! 1584.0530395508): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294740085 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294740085 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 27408.838272095): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (185.96649169922): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (!!!!! 2933.0253601074): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (460.86311340332): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (!!!!! 1144.8860168457): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (279.90341186523): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (!!!!! 1006.1264038086): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (555.03845214844): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (155.92575073242): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (44.107437133789): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (803.94744873047): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (!!!!! 4847.0497131348): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (768.89991760254): SELECT name FROM jos_deeppockets WHERE id=211
138 (53.882598876953): SELECT name FROM jos_deeppockets WHERE id=211
139 (644.20700073242): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (!!!!! 2312.8986358643): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (!!!!! 1350.8796691895): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
142 (!!!!! 5108.8333129883): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
143 (!!!!! 8215.9042358398): TRUNCATE TABLE jos_trademed_module
144 (!!!!! 6887.9127502441): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (!!!!! 4530.9066772461): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294740085 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (!!!!! 4050.9700775146): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (!!!!! 15668.153762817): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (!!!!! 11568.069458008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
149 (!!!!! 5816.9364929199): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
150 (!!!!! 7436.0370635986): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (!!!!! 3633.975982666): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
152 (!!!!! 8182.0487976074): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
153 (!!!!! 4279.8519134521): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294740085 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294740085 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (730.99136352539): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
155 (!!!!! 6051.0635375977): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=211 or channel_id is null)
156 (!!!!! 8867.0253753662): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (!!!!! 1163.0058288574): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
158 (223.15979003906): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294740085 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294740085 AND published='1' LIMIT 1
159 (!!!!! 1055.9558868408): select jos_twitters.link from jos_twitters where cat=10
160 (154.97207641602): select jos_facebook.link from jos_facebook where cat=10
161 (140.90538024902): select jos_google_plus.link from jos_google_plus where cat=10
162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10