Where do research ideas come from? Do they arrive in a thunderbolt eureka moment, or do they start as an observation or hunch, requiring some time to simmer, brew, incubate and grow? Some may evolve from an accidental or serendipitous discovery during a routine process.
Observant operators of the Phoenix MICRON® retinal imaging system may discover incidental ophthalmic findings throughout their imaging of murine eye/brain research. Such was the case for Travis Cossette, Research Assistant III in Dr. Gareth Howell’s Lab at The Jackson Laboratory, Bar Harbor, Maine who had been using the MICRON for just over one year. While performing bright field and fluorescein angiography on a 4-month-old New Zealand Obese mouse (NZO/HlLtJ) he took some time to document a finding he thought was unique.
“NZO inbred mice and strains originating from them develop severe obesity, and are therefore useful for studying obesity and Type 2 diabetes. I had injected the mouse with IP sodium fluorescein and was capturing images during the late phase of the angiogram.” says Travis. “I typically adjust the focus from posterior to anterior to make sure my images at various levels or the retina are sharp, when I noticed unusual vessels coming up through the vitreous. Not only that, I could see circulation within the vessels as well as blood flow in the retinal microvasculature when I focused posteriorly. I was excited to be able to capture a Phoenix MICRON video to share and to dive into the body of research articles to understand what I was looking at. I had difficulty finding any information on my search terms “anomalous retinal vessels in mice” so I reached out to the staff at Phoenix-MICRON, Inc., in Bend, Oregon. They have accumulated a database of over 300 published research publications where the Phoenix MICRON system was used. They recognized what I had documented and were able to direct me to some useful articles. It turns out the vessels are not so anomalous.”
The embryonic eye is filled with a dense network of blood vessels making up the vascular hyaloid system. The vessels function as nutrition for the developing retina and crystalline lens. Unlike humans, where the vessels regress before birth, in mice the hyaloid vasculature starts to regress after birth, with it being generally complete at P21. However, in some situations not all vessels disappear leaving remnants traversing from the optic nerve head up through the vitreous to attach at the posterior surface of the crystalline lens. This is known as persistent fetal vasculature (PFV).
PFV may give rise to the eye disease known as persistent hyperplastic primary vitreous (PHPV) which is a fibrovascular mass. Less severe vessel remnants may include strands, opacities, vessel dragging, pigment clumps and cataracts. These remnants may look like image artifacts such as dried gel on the MICRON lens tip, dust or coupling gel bubbles. PFV anomalies are usually anterior to the retina, therefore changing the focal plane up through the vitreous and crystalline lens like Travis did, may help identify what can look like a blur or spot on the image.
As the academic year is freshly underway, students and researchers have flocked back to labs keen to learn about murine ophthalmology, ask questions, create hypotheses, find answers, share ideas and contribute towards publications. Differentiating image artifacts from ocular abnormalities is an important part of the imaging and research process. Not only is it essential to distinguish artifacts from actual pathology, but the ability to capture what is questionable and share it is a useful educational step. The discussion may lead to improved imaging techniques and a better understanding of ocular morphology. Furthermore, it could germinate the seed of an idea which leads down an exciting path of inspiration and discovery, all started by the observation of that accidental or serendipitous finding during a routine process.
Interested in knowing more about PFV? Take a look at the Phoenix MICRON image examples published in the papers below.
Bret A Moore, Michel J Roux, Lionel Sebbag, Ann Cooper et al (2018) A Population Study of Common Ocular Abnormalities in C57BL/6N rd8 Mice. Invest Ophthalmol Vis Sci May 1;59(6):2252-2261. DOI: 10.1167/iovs.17-23513.
Zhongxiao Wang, Chi-Hsiu Liu, Shuo Huang, Jing Chen (2019) Assessment and Characterization of Hyaloid Vessels in Mice. J Vis Exp 15;(147):10.3791/59222. doi: 10.3791/59222.