Vascular Lakes are pools of blood which appear in Uveal Melanoma (UM) tumours, very little is known about them or their contribution towards the tumour’s progression. This project will explore whether Vascular lakes have any prognosis indicators, provide any nutrients to the tumours or provide a pathway for the tumour to escape. But before getting into the nitty-gritty details of vascular lakes, it’s best we have a brief overview of what UM is!
UM is a rare form of cancer with around 6 million cases diagnosed a year. It is the most common adult intraocular tumour, most of which are single tumours confined to one eye. The aetiology of UM is unknown; unlike melanomas that occur in the skin, there is no link between the causation of UM and UV light. UM is predominantly found within the choroid but can also occur in the iris and ciliary body (Figure 1). The Risk of developing UM increases with age, in addition, it is more common in Caucasians and is up to three times more likely to occur in the blue iris than it is in brown. Symptoms of UM include blurred vision; visual field lost; floating light across the visual field and pain.
Locations UM can develop (Mayo Clinic, 2017)
Primary UM has many therapeutic options, including various forms of radiotherapy, surgery and phototherapy all of which can be very successful. Despite this, around 50% of UM patients go on to develop metastasis which usually occurs in the liver and is often fatal. Although there are many prognostic markers which allows for patients to be recognised as being high or low risk for metastatic UM, there is no definitive prognosis for patients. These markers are of high importance to improve patient care and prolong lives.
This is where our research into vascular lakes comes in, we’re going to be looking into the number and size of these lakes to see if they have any prognostic value. Vascular lakes appear to be immature blood vessels which haven’t developed any tissue lining. To test this, we will be staining histological images of eyes with UM tumours (Figure 2) to pick up any endothelial cells which make up the tissue lining of mature blood vessels. Then, using image analysis, we will classify vascular lakes depending on whether they have a tissue layer of cells surrounding them or not. Next, we want to know if these lakes go anywhere such as into other blood vessels, or whether they are just pits of plasma and blood. To help answer this we will use Electron Microscopy (EM) which will allow us to see around the vascular lakes. EM will also help us confirm that there is no tissue surrounding the lakes which can’t be seen simply from the histological slides. Now that all the image analysis has been done, we want to know whether these lakes have any nutritional value to the help the tumour to grow, or if they give the tumour a migration route into the bloodstream triggering the development of metastatic UM. To do this we will compare the image analysis results with patient’s clinical data to see if they correlate with the prognosis of patients. Phew! That’s a lot of questions on Vascular Lakes! But were not stopping there…
Histological image of eye with Choroidal Melanoma (left), Vascular Lake within the Choroidal Melanoma (right)
UM is believed to be a cancer arising from uveal melanocytes, but it’s not known how melanin behaves around tumours; such as whether the amount of melanin increases or clusters around tumours, or if the amount present in the eye changes with age. So, we’re going to explore melanin’s role in UM by using sections of the choroid with no tumour as a control and comparing it against choroidal tumours to see if there are any patterns or changes in the melanin. We’ll be using commercial image analysis software provided by our industrial partner, Definiens, who are leading experts in image analysis focusing on immuno-oncology. This section of the research focuses on what role melanin has in patient’s diagnosed with UM and whether it can be used as a predictor for prognosis in patients.
With all this talk about the importance of prognosis in patients comes the question: What about the people who go on to develop Metastatic UM? As we know, early detection in patients with high risk helps prolong their survival. The Liverpool Ocular Oncology Research Group (LOORG) are currently using UM cell lines to grow tumours in their laboratory with the hope of being able to see if targeted drug treatments can destroy the cancer cells. To predict the outcome of this, we are going to develop a mathematical model based on the LOORG UM tumours. This model will then go on to predict whether nanoparticles have the potential to penetrate through these tumours to deliver therapeutic drugs. Targeted therapy has many benefits to patients as the treatment targets cancer cells only and leaving healthy cells unharmed.
You can see more about LOORG and their research here