## 3 Discussion  
Lipid metabolism and the circadian machinery are closely interrelated. Disruption of circadian rhythms in glaucoma is caused by progressive damage to RGCs [18; 19; 20; 39; 40; 41], particularly to intrinsically photosensitive retinal ganglion cells, ipRGCs [22; 42]. Altered lipids were repeatedly shown to be associated with glaucoma [36; 37] and commonly considered as one of the putative causative co-factors. However, an alternate concept can be proposed, linking altered lipid metabolism with compromised light perception and concomitant circadian misalignment. Indeed, several recent works demonstrated that circadian disruption due to compromised light perception, or diminished amplitude of circadian light signaling may affect metabolism [1; 1; 43; 44]. RGC loss in glaucoma diminishes the amount of daylight perceived and transferred to the relevant brain regions, including the SCN. Our results reported herein suggest that changes in serum lipids could be integrated into a vicious circle caused by circadian disruptions due to glaucomatous damage to RGCs [21]. One may assume a causal relationship between progressively impaired daylight photic signaling and glaucoma progression and specific alterations of lipid metabolism, since changes in light perception may influence circadian lipid metabolism that may involve, \begin{table}
\begin{tabular}{l c} \hline
**Gene Polymorphisms** & _p-Value for Effect Significance; ANOVA for LDL-C MEG_ \\ \hline
**CLOCK rs1801260 3111T/C** & **0.023** \\ \hline _PER2_ rs6431590 & 0.507 \\ \hline _PER3_ VNTR & 0.644 \\ \hline _CRY1_ rs12820777 & 0.169 \\ \hline _MTNR1A_ rs34532313 & 0.656 \\ \hline _MTNR1B_ rs10830963 & 0.338 \\ \hline _GNB_ rs5443 & 0.814 \\ \hline \end{tabular}
\end{table} 
Table 2: Morning-evening gradients (MEGs) of low-density lipid cholesterol (LDL-C) depended on studied polymorphic variants of the biological clock, melatonin receptors, and G-protein genes in primary-open glaucoma patients (n = 19). Significant correlations are bold. Figure 5: Evening rise in low-density lipid cholesterol, LDL-C was linked to CLOCK_3111 (rs1801260) TT genotype. Kruskal–[PERSON], KW-H (1;18) = 5.500; \(p\) = 0.019. n = 18.; TC = 12; TT = 6 °: \(p\) < 0.05.  
or not involve changes in daily food consumption. Dimmer diurnal light, similarly to light at night, reduces the amplitude of ambient light, the main circadian synchronizer, thereby weakening circadian entrainment and altering lipid metabolism. Indeed, circadian disruption is caused by clock gene mutations [1; 45; 46], or changes in ambient light conditions [1; 43; 44], which have numerous metabolic consequences. These studies suggest that diminished amplitude of light signaling between day and night, including dim light at night, may cause lipid metabolism alteration resembling what we found with progressive loss of RGCs in glaucoma. Contrary to light-at-night, when the circadian amplitude is diminished due to excess light when light should be avoided, in glaucoma patients, the circadian amplitude is diminished due to light deficit during the daytime. Since RGCs are necessary to convey light signals to the central circadian oscillator, their progressive loss reduces the effectiveness of the synchronizing role of circadian rhythms by the environmental light-dark cycle. In this study, changes in lipid metabolism were not only associated with RGC loss, but they also depended on their daytime pattern. Morning values of HDL-C and TG gradually increased with RGC loss. On the contrary, morning LDL-C values correlated only weakly with RGC loss. A stronger correlation was found in the evening, which was associated with a larger morning-evening gradients (MEGs). Moreover, MEGs were influenced by both RGC loss and _CLOCK_ gene polymorphism. Current knowledge of circadian rhythmicity of serum lipids is scarce and varies between populations and depending on study conditions. Twenty-four-hour profiles of serum lipids vary among individuals.