Multi Image (Same Noise Realization) Denoising
For me, if all you want to deal with is the possible 'debris in the optics,' why not get a reference background image? This will help you to easily identify which are 'noise' caused by your optics. Assume you can get a perfect background, namely everything remains the same except for your cells ( maybe you can get this by taking another image after removing all cells ), then simply subtract the background image from the original one will work.