HPPD symptoms as disruption of the retinal night/day modes modulated by dopamine

[Cotcha Yankinov]

Using a model of retinal tyrosine hydroxylase knockout, it was found that "retinal dopamine is necessary for high-resolution, light-adapted vision, mediated through dopamine D1 and D4 receptors" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400466/)

"Light-adapted vision is mediated by the cone system of the retina and in the natural environment occurs during the light of the day when high luminance and high contrast provide the basis for high-resolution vision. Our results indicate that dopamine reconfigures the retina for day-time vision enhancing contrast sensitivity and high-spatial resolution.

Retinal dopamine signaling is elevated in the circadian day, either as a consequence of rhythmic dopamine secretion driven by the retinal circadian clock (Witkovsky, 2004), or as a result of diurnal or circadian rhythms in dopamine D4 receptor gene expression (Bai et al., 2008; Jackson et al., 2011; Klitten et al., 2008; Storch et al., 2007).

D1 receptors modulate horizontal cell coupling through gap junctions in a wide range of species, including mammals and primates (He et al., 2000; Xin and Bloomfield, 1999; Zhang et al., 2011), acting to uncouple horizontal cells, restrict current flow across their electrical synapses, and shrink their receptive fields.

Although the relationship between horizontal cell receptive fields and the center-surround structure of ganglion cell receptive fields is still poorly understood, a conventional interpretation is that horizontal cells contribute to ganglion cell inhibitory surrounds (but see (Dedek et al., 2008)). Therefore, a loss of dopamine signaling could expand horizontal cell receptive fields through increased coupling, and in turn, expand ganglion cell receptive field surrounds to shift the tuning of ganglion cell responses toward lower spatial frequencies.

In retina D4 receptors are principally concentrated in cone photoreceptors where they are known to affect cAMP metabolism, gene expression and rod-cone gap junctional coupling (Cohen et al., 1992; Jackson et al., 2011; Ribelayga et al., 2008). They play a critical role in circadian modulation of rod-cone coupling, enhancing transmission of rod signals into cones and cone pathways in the night-phase of retinal circadian rhythms when dopamine is low (Ribelayga et al., 2008).

Increased rod-cone coupling in the absence of dopamine may shunt cone light responses into rods under rod-saturating backgrounds, reducing the light-adapted ERG b-wave. Similarly, the sharing of rod and cone signals through enhanced coupling in the absence of dopamine may reduce the CSF of ganglion cell centers, and thus dampen the overall contrast sensitivity.

In conclusion, we have described a mouse model in which retinal dopamine is selectively depleted and which reveals specific deficits in light-adapted vision. This mouse model should be useful in delineating the underlying mechanisms by which retinal dopamine reconfigures retinal circuits according to circadian time and background illumination."



Given the regulation of retinal ganglion night-day modes by dopamine, its prudent to mention that dopamine antagonists are known to worsen HPPD symptoms (at first), while COMT inhibitors are known to decrease HPPD symptoms.

5-HT2A receptors have been found in the photoreceptor and rod bipolar cells of the rabbit and there is evidence of 5-HT2A expression on cone bipolar cells of mice. There is also evidence of reciprocal connections between the DRN and retinal cells in monkeys (Cebus Apella). There seems to be some in evidence of LSD affecting human retina; "Ostfeld and colleagues detected changes in both the ERG and dark adaptation curves of individuals receiving hallucinogenic doses of LSD."

In addition, while diphenhydramine abuse is an anecdotally well known cause of visual snow and HPPD symptoms, muscarinic receptors have effects on retinal ganglion cells "The activation and blockade of muscarinic acetylcholine receptors (mAChRs) affects retinal ganglion cell light responses and firing rates" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868487/)

The 5-HT2A antagonist antidepressant Nefazodone has been reported to cause HPPD symptoms through effects on the retina that can be detected with multifocal electroretinogram.

Some people report HPPD symptoms at night, and HPPD sufferers certainly report increased visuals in low-lighting even though they often have poor night-vision. With other symptoms like sensitivity to light, afterimages and so forth, maybe HPPD is an issue with the retinal ganglion cell's modes, with reduced contrast playing a role in visual snow?

Any thoughts are appreciated.

 

[d1nach]

Not gunna lie I tried reading that in this state and most of it went over my head. Lol

However maybe this might help given the option. I keep my room with all the lights off and just one hallway light even In the day I take alot of stimulants nicotine and diphenhydramine. Normal brightness hurts my eyes and I like it where everything I'm looking at is visible but everything else is dark enough I can't really see it

 

[serotonin2A]

These effects wouldn't explain HPPD. All the HPPD symptoms, as well as the visual effects of LSD, reflect higher level processes that are known to occur in visual cortex. If HPPD simply involved a loss of visual acuity then such an explanation would make sense, but HPPD sufferers don't experience a loss of vision.

Nefazadone can produce some HPPD-like symptoms, but that isn't usually asdociated with a loss of visual acuity. Thus, the published case os not reflective of HPPD. It may be a rare case of HPPD sufferer who also experienced retinal disease.

 

[d1nach]

I see snow everyday like looking on my phone it looks like tiny specs are pulsating off I always just shock it off as intense dopamine release because on Nat Geo they said heavy crack or cocaine users get it if they do alot at their peak. Never thought of it as a hallucination because I'm not seeing anything not supposed to be there same with like double vision or size distortion. As just errors in sensation.

 

[Cotcha Yankinov]

These effects wouldn't explain HPPD. All the HPPD symptoms, as well as the visual effects of LSD, reflect higher level processes that are known to occur in visual cortex. If HPPD simply involved a loss of visual acuity then such an explanation would make sense, but HPPD sufferers don't experience a loss of vision.

Nefazadone can produce some HPPD-like symptoms, but that isn't usually asdociated with a loss of visual acuity. Thus, the published case os not reflective of HPPD. It may be a rare case of HPPD sufferer who also experienced retinal disease.

I hesitated in mentioning HPPD versus visual snow because I was thinking that this theory would be more applicable to visual snow than ie geometric patterns, visual snow seemingly being a much more frequent complaint of ecstasy/diphenhydramine abusers rather than genuine HPPD.

I vividly remember getting visual snow and other artifacts in the dark when I was drug naïve and others have reported this, but I hope I'm not tunnel visioning on those accounts too much.

"Similarly, the sharing of rod and cone signals through enhanced coupling in the absence of dopamine may reduce the CSF of ganglion cell centers, and thus dampen the overall contrast sensitivity."

I hope I'm understanding this correctly - would this effect be expected to alter vision experience towards the images on the left?





In this photo of contrast variation, the middle-left image is incredibly reminiscent of visual snow/grainy vision I have experienced after diphenhydramine/ecstasy abuse with acute worsening during sleep deprivation (there was not only visual snow like artifacts, but there was mild shift in color like depicted above - I understand that some optic neuritis could also account for this). Could this visual experience be due to dysfunction of retinal ganglion?


However I think the other visual phenomenon of HPPD, like geometric patterns and occasionally reported akinetopsia, could not be explained by issues directly with the retina ganglion.

 

[serotonin2A]

I hesitated in mentioning HPPD versus visual snow because I was thinking that this theory would be more applicable to visual snow than ie geometric patterns, visual snow seemingly being a much more frequent complaint of ecstasy/diphenhydramine abusers rather than genuine HPPD.

I vividly remember getting visual snow and other artifacts in the dark when I was drug naïve and others have reported this, but I hope I'm not tunnel visioning on those accounts too much.

"Similarly, the sharing of rod and cone signals through enhanced coupling in the absence of dopamine may reduce the CSF of ganglion cell centers, and thus dampen the overall contrast sensitivity."

I hope I'm understanding this correctly - would this effect be expected to alter vision experience towards the images on the left?





In this photo of contrast variation, the middle-left image is incredibly reminiscent of visual snow/grainy vision I have experienced after diphenhydramine/ecstasy abuse with acute worsening during sleep deprivation (there was not only visual snow like artifacts, but there was mild shift in color like depicted above - I understand that some optic neuritis could also account for this). Could this visual experience be due to dysfunction of retinal ganglion?


However I think the other visual phenomenon of HPPD, like geometric patterns and occasionally reported akinetopsia, could not be explained by issues directly with the retina ganglion.

I don't think the effect of contrast variation is the same as visual snow. Visual snow is really noise in the visual field. By contrast, reducing contrast alters the dynamic range of an image but it shouldn't make images grainy.

Don't forget that the activation of small numbers of retinal ganglion cells is subperceptual -- cells in V1 can be activated by images of gratings that are too narrow to be perceived. That means that retinal noise would likely be imperceptible.

 

[Tranced]

My visual snow effectively consists of my vision being made up of small red/pink/purple dots, most especially prominent at a night time.

The only way that I find it effecting anything through the day is that I can see a mild trace of them on say a white wallpaper, which seems to slightly alter and colour the image.

 

[Kdem]

Interesting, thank you.

 

[Cotcha Yankinov]

I don't think the effect of contrast variation is the same as visual snow. Visual snow is really noise in the visual field. By contrast, reducing contrast alters the dynamic range of an image but it shouldn't make images grainy.

Don't forget that the activation of small numbers of retinal ganglion cells is subperceptual -- cells in V1 can be activated by images of gratings that are too narrow to be perceived. That means that retinal noise would likely be imperceptible.

Okay thanks for the input, I guess we shall discard this theory. Especially considering many of the visual snow reporters (from ecstasy use) I have talked with report tinnitus as well - but I'm curious about the worsening HPPD symptoms in darkness (as a poster above mentions too) and the worsening of tinnitus with silence (and improvement with the use of a fan etc).

The three components (that are not entirely exclusive) that come to my mind are

1. Gain
2. Competition-inhibition
3. Attention

Theory 1. During low light, the gain of the visual system increases and this amplifies visual snow - during silence, the gain of the audio system increases and this amplifies tinnitus.

Theory 2. During nighttime, there is reduced competition between visual signal from a well-lit environment vs. internally generated noise, thus the noise rises above perceptual threshold due to reduced inhibition of noise by genuine signal.

Theory 3. Reduced genuine visual/audio signal results in an increased attention to noise. I mention this one because many people who have not had adverse effects are convinced that people are simply paying more attention to their visual/audio fields, and that they had the HPPD symptoms all along but are just now really noticing them in a hypochondriac-esque way.

Although I think 3. is most applicable to tinnitus and couldn't explain the visual symptoms - to this day my tinnitus can become quite loud if I focus on it.

 

[serotonin2A]

It makes sense that the symptoms would increase in the dark. The symptoms are less noticable if there is substantial sensory input. The same thing happens with LSD-induced visual patterns.

Basically its a signal-noise issue.