The unique chromatin distribution in the rod cells is a deviation from an evolutionary highly conserved pattern (Solovei 2016). It has sparked the interest of the scientists to study the unique epigenetic landscape to understand the regulatory principles of genome organisation. This mechanism has recently been described as a self-organised restructuring of the denser heterochromatin, phase separating into a central compact globular aggregate in the absence of its interactions with the nuclear lamina (Falk et al 2018). Also, robust differentiation signals acting on the neuronal precursors ensure the unique genetic make-up of the rods (Hiler 2015).
The deviation from a conventional arrangement, however seems to come with its costs. The DNA repair machinery is shown to be impaired in the rods (Frohns 2014). The rods are ss pliant and highly susceptible to apoptosis under stress (Dyer, 2016). Their reprogrammability is the lowest among the retinal cells (Wang 2018).In light of the findings presented in the thesis, it can be argued that these costs are compensated by the gain in the optical properties of the tissue resulting in the ultimate increase in the visual sensitivity for mice and other nocturnal mammals.
It is worth mentioning that, in addition to the chromatin distribution, the overall fraction of heterochromatin to euchromatin is shown to be different for the photoreceptors, constituting a 50:50 proportions as against a typical 90% dominance of euchromatin in other cell types (Wang 2018). The greater mass of the heterochromatin allows for a larger aggregate to form resulting in a more closed and compact packing resulting in an overall reduced volume specific scattering (cref). When comparing the MTF of the WT and TG-LBR ONL, representation of the ratio of the transfer function yields a curve very similar to a sharpening filter (cref).
Fitting a model to such a function (ref) yields parameters that describe the operating range of the filter close to the visual acuity of mouse. Given the improved optics of the inverted architecture, it poses a question as to why the architecture is exclusive to nocturnal mammals (ref).Visibility and detectability of an object by an imaging system or a detector array is a function of image contrast, signal to noise, size of the detector, amount of light and the quantum efficiency of the detector described by the following relation (Rose 1948). Resolution= C/k √(n/A) η (1)C=contrast, n=number of photons, A=total area of detector, k=signal to noise threshold k∈[3,5], η=quantum efficiency.For typical values of area of mouse retina and reported signal to noise and quantum efficiency values for rod photoreception (ref) we can construct a plot as shown in figure.
It can be seen that the resolution dictated by the above relationship is around 20cycles/deg for an illumination of about 100Lux (photopic vision). This value is well beyond the visual acuity range of mouse. Thus, any changes in the contrast (compare WT vs TG-LBR retina) will not have an effect in the physiological response of the mouse. The critical illumination is of the order of 100 mLux (scotopic vision) for mouse below which changes in the contrast transmission varied within the visual acuity range. This transition is experimentally observed in the behaviour of the animals where, there was no significant differences between the two mouse types for photopic illumination while the differences begin to show only at scotopic conditions.
Similarly for a diurnal mammal such as a human the critical illumination is about 25Lux which well below the typical dwelling area illumination during the day. Moreover, there are additional morphological features such as the fovea that is responsible for high acuity vision in higher mammals where, the inner retinal layers are pushed aside to giving light access to the photoreceptor cells. We thus can appreciate the need for the nuclear adaptation.