cGMP-PKG dependent transcriptome in normal and degenerating retinas: Novel insights into the retinitis pigmentosa pathology

A Potential Role of Cyclic Dependent Kinase 1 (CDK1) in Late Stage of Retinal Degeneration

“…effect on CDK1 expression after 2 days of PKG inhibition is in contrast to the lack of effect on TUNEL staining from the same treatment [6]. This may be related to the fact that while CDK1 expression according to our overlap analyses is increased late in the degeneration process, it is still early enough to be affected by the PKG inhibition before this reduces TUNEL staining.…”

“…Compared to the non-treated counterparts, we could not find any alteration of CDK1 expression after 2 h of PKG inhibition, while it was evidently less expressed after 2 days and 4 days of treatment ( Figure 2 ). We note that the effect on CDK1 expression after 2 days of PKG inhibition is in contrast to the lack of effect on TUNEL staining from the same treatment [ 6 ]. This may be related to the fact that while CDK1 expression according to our overlap analyses is increased late in the degeneration process, it is still early enough to be affected by the PKG inhibition before this reduces TUNEL staining.…”

“…A CDK1 functional study indicated that CDK1 upregulates mitochondrial respiration to drive the cell cycle, whose progression requires a large amount of energy [ 13 ]. It is universally accepted that photoreceptors are one of the most energy demanding cells [ 14 ], and we recently proposed that PKG inhibition may alleviate retinal degeneration via the positive regulation of oxidative phosphorylation [ 6 ]. As a speculation, the progressively decreased CDK1 expression within photoreceptors after 2 and 4 days of treatment could then mean that the oxidative stress of photoreceptors was to some extent alleviated after PKG inhibition, relieving CDK1 from its function to upregulate mitochondrial respiration.…”

“…Retinal explants were generated from P5 rd1 retinas, as previously described [ 6 ]. Culturing membrane inserts with the explants were put into six-well culture plates, with 1.5 mL serum-free medium in each well.…”

Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration

“…The M2 subtype of pyruvate kinase (PKM2) has been shown to be expressed within photoreceptors ( Rajala et al, 2018 ) and our previous transcriptome research ( Zhou et al, 2021 ), where we modulated the cGMP-PKG system in retinal explants, showed a lower expression of the PKM2 gene after PKG activation in wild-type (WT) retinas. This pointed to the possibility that PKM2 may be repressed by the high cGMP-PKG activity within RP photoreceptors.…”